Trial Outcomes & Findings for Trial of Panobinostat in Children With Diffuse Intrinsic Pontine Glioma (NCT NCT02717455)

Last Updated: 2024-04-25

Results Overview

DLTs were defined as adverse events that were at least possibly related to panobinostat that occurred during the first 4 weeks of therapy regardless of expectedness. Hematologic DLTs included grade 4 thrombocytopenia, grade 3 thrombocytopenia with bleeding, grade 3 thrombocytopenia that occurs twice within a treatment course, myelosuppression that causes greater than a 14-day delay between treatment courses, grade 4 neutropenia, grade 3 or 4 febrile neutropenia. Non-hematologic DLTs included any grade 3 or greater non-hematologic toxicities with a few exclusions (such as grade 3 nausea/vomiting that is responsive to antiemetics and that resolves to grade 2 or lower within 5 days, etc.), any grade 2 non-hematological toxicity that persists for more than 7 days and is considered sufficiently medically significant or sufficiently intolerable by patients, and any panobinostat-related non-hematological toxicity that results in a delay of treatment \> 14 days between treatment courses.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

53 participants

Primary outcome timeframe

4 weeks

Results posted on

2024-04-25

Participant Flow

Patients between 2 and 22 years of age (\>= 2, \< 22) at the time of enrollment were enrolled at Pediatric Brain Tumor Consortium (PBTC) member institutions. The first patient on study was enrolled on June 28, 2016, and the last patient was enrolled on November 10, 2021.

Patients with recurrent/progressive diffuse intrinsic pontine glioma (DIPG) were enrolled on stratum 1, and patients with non-progressed DIPG or H3K27M+ thalamic diffuse malignant glioma (DMG) were enrolled on stratum 2.

Participant milestones

Participant milestones
Measure	Stratum 1, Dose Level 1 (10 mg/m^2) Recurrent or progressive DIPG patients received panobinostat orally every other day, 3 times per week at 10 mg/m\^2/day for three weeks on, one week off (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 1, Dose Level 2 (16 mg/m^2) Recurrent or progressive DIPG patients received panobinostat orally every other day, 3 times per week at 16 mg/m\^2/day for three weeks on, one week off (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 1 (16 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 16 mg/m\^2/day for every other week (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 2 (22 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 22 mg/m\^2/day for every other week (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 3 (28 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 28 mg/m\^2/day for every other week (1course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 4 (36 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 36 mg/m\^2/day for every other week (1course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	13	6	3	12	12	7
Overall Study COMPLETED	10	5	3	6	7	2
Overall Study NOT COMPLETED	3	1	0	6	5	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Stratum 1, Dose Level 1 (10 mg/m^2) Recurrent or progressive DIPG patients received panobinostat orally every other day, 3 times per week at 10 mg/m\^2/day for three weeks on, one week off (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 1, Dose Level 2 (16 mg/m^2) Recurrent or progressive DIPG patients received panobinostat orally every other day, 3 times per week at 16 mg/m\^2/day for three weeks on, one week off (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 2 (22 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 22 mg/m\^2/day for every other week (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 3 (28 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 28 mg/m\^2/day for every other week (1course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 4 (36 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 36 mg/m\^2/day for every other week (1course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.
Overall Study Adverse Event	1	0	2	2	2
Overall Study Withdrawal by Subject	1	1	2	2	1
Overall Study Death	1	0	0	1	0
Overall Study Did not receive study drug	0	0	1	0	1
Overall Study Extended delay in start of next cycle for reasons unrelated to treatment	0	0	0	0	1
Overall Study Patient off-treatment for other complicating disease	0	0	1	0	0

Baseline Characteristics

Trial of Panobinostat in Children With Diffuse Intrinsic Pontine Glioma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Stratum 1, Dose Level 1 (10 mg/m^2) n=13 Participants Recurrent or progressive DIPG patients received panobinostat orally every other day, 3 times per week at 10 mg/m\^2/day for three weeks on, one week off (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 1, Dose Level 2 (16 mg/m^2) n=6 Participants Recurrent or progressive DIPG patients received panobinostat orally every other day, 3 times per week at 16 mg/m\^2/day for three weeks on, one week off (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 1 (16 mg/m^2) n=3 Participants Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 16 mg/m\^2/day for every other week (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 2 (22 mg/m^2) n=12 Participants Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 22 mg/m\^2/day for every other week (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 3 (28 mg/m^2) n=12 Participants Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 28 mg/m\^2/day for every other week (1course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 4 (36 mg/m^2) n=7 Participants Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 36 mg/m\^2/day for every other week (1course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Total n=53 Participants Total of all reporting groups
Age, Continuous	5.9 years n=5 Participants	10.5 years n=7 Participants	13.6 years n=5 Participants	8.0 years n=4 Participants	7.8 years n=21 Participants	6.7 years n=10 Participants	7.9 years n=115 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	8 Participants n=4 Participants	7 Participants n=21 Participants	5 Participants n=10 Participants	35 Participants n=115 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants	5 Participants n=21 Participants	2 Participants n=10 Participants	18 Participants n=115 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	2 Participants n=21 Participants	4 Participants n=10 Participants	13 Participants n=115 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	8 Participants n=4 Participants	7 Participants n=21 Participants	3 Participants n=10 Participants	32 Participants n=115 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants	3 Participants n=21 Participants	0 Participants n=10 Participants	8 Participants n=115 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	4 Participants n=115 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=10 Participants	4 Participants n=115 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	6 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	6 Participants n=21 Participants	7 Participants n=10 Participants	30 Participants n=115 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	6 Participants n=4 Participants	5 Participants n=21 Participants	0 Participants n=10 Participants	15 Participants n=115 Participants

PRIMARY outcome

Timeframe: 4 weeks

Population: Patients who were evaluable for DLT assessment were included in this analysis. Of all 53 patients enrolled, 7 patients were not evaluable for DLT assessment: 4 patients received less than required dose of study drug, 2 patients did not start protocol therapy, and 1 patient had insufficient labs to monitor for DLTs.

Outcome measures

Outcome measures
Measure	Stratum 1, Dose Level 1 (10 mg/m^2) n=12 Participants Recurrent or progressive DIPG patients received panobinostat orally every other day, 3 times per week at 10 mg/m\^2/day for three weeks on, one week off (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 1, Dose Level 2 (16 mg/m^2) n=5 Participants Recurrent or progressive DIPG patients received panobinostat orally every other day, 3 times per week at 16 mg/m\^2/day for three weeks on, one week off (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 1 (16 mg/m^2) n=3 Participants Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 16 mg/m\^2/day for every other week (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 2 (22 mg/m^2) n=10 Participants Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 22 mg/m\^2/day for every other week (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 3 (28 mg/m^2) n=11 Participants Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 28 mg/m\^2/day for every other week (1course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 4 (36 mg/m^2) n=5 Participants Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 36 mg/m\^2/day for every other week (1course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.
Number of Patients Who Experienced Dose Limiting Toxicities (DLTs)	0 Participants	2 Participants	0 Participants	1 Participants	4 Participants	3 Participants

PRIMARY outcome

Timeframe: 4 weeks

Population: Patients who were enrolled on stratum 1 and were evaluable for dose finding assessment were used to determine the MTD for stratum 1. Of 19 patients enrolled on stratum 1, 2 patients were not evaluable for dose finding assessment due to receiving less than required dose of study drug. The remaining 17 patients were used to determine the MTD for stratum I.

The MTD of panobinostat was defined as the dose at which the continual reassessment method (CRM) estimated that 25% of patients were expected to experience DLTs. Stratum 1 consisted of recurrent or progressive diffuse intrinsic pontine glioma (DIPG) patients who were treated with the "3 times/week, three weeks on, one week off" schedule (1 course = 28 days).

Outcome measures

Outcome measures
Measure	Stratum 1, Dose Level 1 (10 mg/m^2) n=17 Participants Recurrent or progressive DIPG patients received panobinostat orally every other day, 3 times per week at 10 mg/m\^2/day for three weeks on, one week off (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 1, Dose Level 2 (16 mg/m^2) Recurrent or progressive DIPG patients received panobinostat orally every other day, 3 times per week at 16 mg/m\^2/day for three weeks on, one week off (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 1 (16 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 16 mg/m\^2/day for every other week (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 2 (22 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 22 mg/m\^2/day for every other week (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 3 (28 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 28 mg/m\^2/day for every other week (1course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 4 (36 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 36 mg/m\^2/day for every other week (1course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.
Maximum Tolerated Dose (MTD) of Panobinostat in Stratum 1	10 mg/m^2/day	—	—	—	—	—

PRIMARY outcome

Timeframe: 4 weeks

Population: Patients who were enrolled on stratum 2 and were evaluable for dose finding assessment were used to determine the MTD for stratum 2. Of 34 patients enrolled on stratum 2, 5 patients were not evaluable due to: receiving less than required dose of study drug (2), disease progression before active treatment (1), withdrawal/refusal prior to protocol therapy (1), and insufficient labs to monitor for dose-limiting toxicities (1). The remaining 29 patients were used to determine the MTD for stratum 2.

The MTD of panobinostat was defined as the dose at which the continual reassessment method (CRM) estimated that 25% of patients were expected to experience DLTs. For Stratum 2, non-progressed DIPG or H3K27M+ thalamic diffuse malignant glioma (DMG) patients who completed conventional radiation treatment were eligible. All patients enrolled on this stratum had DIPG tumors and were treated with the "3 times/week, every other week" schedule (1 course = 28 days).

Outcome measures

Outcome measures
Measure	Stratum 1, Dose Level 1 (10 mg/m^2) n=29 Participants Recurrent or progressive DIPG patients received panobinostat orally every other day, 3 times per week at 10 mg/m\^2/day for three weeks on, one week off (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 1, Dose Level 2 (16 mg/m^2) Recurrent or progressive DIPG patients received panobinostat orally every other day, 3 times per week at 16 mg/m\^2/day for three weeks on, one week off (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 1 (16 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 16 mg/m\^2/day for every other week (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 2 (22 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 22 mg/m\^2/day for every other week (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 3 (28 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 28 mg/m\^2/day for every other week (1course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 4 (36 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 36 mg/m\^2/day for every other week (1course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.
Maximum Tolerated Dose (MTD) of Panobinostat in Stratum 2	22 mg/m^2/day	—	—	—	—	—

PRIMARY outcome

Timeframe: Up to day 3

Population: Patients who had PK samples collected and had Vd data available were included in this analysis.

Plasma samples for pharmacokinetic (PK) analysis were drawn at pre-dose and at 0.5, 1, 2, 4, 8 (±1), 24 (±4) hours after the first dose of panobinostat, as well as prior to the second dose on Course 1 Day 3. Volume of distribution (Vd) was estimated using a noncompartmental method.

Outcome measures

Outcome measures
Measure	Stratum 1, Dose Level 1 (10 mg/m^2) n=10 Participants Recurrent or progressive DIPG patients received panobinostat orally every other day, 3 times per week at 10 mg/m\^2/day for three weeks on, one week off (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 1, Dose Level 2 (16 mg/m^2) n=5 Participants Recurrent or progressive DIPG patients received panobinostat orally every other day, 3 times per week at 16 mg/m\^2/day for three weeks on, one week off (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 1 (16 mg/m^2) n=3 Participants Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 16 mg/m\^2/day for every other week (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 2 (22 mg/m^2) n=7 Participants Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 22 mg/m\^2/day for every other week (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 3 (28 mg/m^2) n=7 Participants Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 28 mg/m\^2/day for every other week (1course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 4 (36 mg/m^2) n=4 Participants Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 36 mg/m\^2/day for every other week (1course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.
Volume of Distribution (Vd)	1704 L Standard Deviation 827	2135 L Standard Deviation 1268	3358 L Standard Deviation 1136	2141 L Standard Deviation 906	1967 L Standard Deviation 455	2487 L Standard Deviation 2760

PRIMARY outcome

Timeframe: Up to day 3

Population: Patients who had PK samples collected and had Kel data available were included in this analysis.

Plasma samples for pharmacokinetic (PK) analysis were drawn at pre-dose and at 0.5, 1, 2, 4, 8 (±1), 24 (±4) hours after the first dose of panobinostat, as well as prior to the second dose on Course 1 Day 3. Elimination rate (Kel) was estimated using a noncompartmental method.

Outcome measures

Outcome measures
Measure	Stratum 1, Dose Level 1 (10 mg/m^2) n=10 Participants Recurrent or progressive DIPG patients received panobinostat orally every other day, 3 times per week at 10 mg/m\^2/day for three weeks on, one week off (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 1, Dose Level 2 (16 mg/m^2) n=5 Participants Recurrent or progressive DIPG patients received panobinostat orally every other day, 3 times per week at 16 mg/m\^2/day for three weeks on, one week off (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 1 (16 mg/m^2) n=3 Participants Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 16 mg/m\^2/day for every other week (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 2 (22 mg/m^2) n=7 Participants Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 22 mg/m\^2/day for every other week (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 3 (28 mg/m^2) n=7 Participants Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 28 mg/m\^2/day for every other week (1course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 4 (36 mg/m^2) n=4 Participants Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 36 mg/m\^2/day for every other week (1course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.
Elimination Rate (Kel)	0.059 per hour Standard Deviation 0.024	0.065 per hour Standard Deviation 0.013	0.047 per hour Standard Deviation 0.003	0.057 per hour Standard Deviation 0.012	0.047 per hour Standard Deviation 0.006	0.066 per hour Standard Deviation 0.017

PRIMARY outcome

Timeframe: Up to day 3

Population: Patients who had PK samples collected and had t1/2 data available were included in this analysis.

Plasma samples for pharmacokinetic (PK) analysis were drawn at pre-dose and at 0.5, 1, 2, 4, 8 (±1), 24 (±4) hours after the first dose of panobinostat, as well as prior to the second dose on Course 1 Day 3. Half-life (t1/2) was estimated using a noncompartmental method.

Outcome measures

Outcome measures
Measure	Stratum 1, Dose Level 1 (10 mg/m^2) n=10 Participants Recurrent or progressive DIPG patients received panobinostat orally every other day, 3 times per week at 10 mg/m\^2/day for three weeks on, one week off (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 1, Dose Level 2 (16 mg/m^2) n=5 Participants Recurrent or progressive DIPG patients received panobinostat orally every other day, 3 times per week at 16 mg/m\^2/day for three weeks on, one week off (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 1 (16 mg/m^2) n=3 Participants Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 16 mg/m\^2/day for every other week (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 2 (22 mg/m^2) n=7 Participants Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 22 mg/m\^2/day for every other week (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 3 (28 mg/m^2) n=7 Participants Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 28 mg/m\^2/day for every other week (1course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 4 (36 mg/m^2) n=4 Participants Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 36 mg/m\^2/day for every other week (1course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.
Half-life (t1/2)	13.0 hour Standard Deviation 4.0	11.0 hour Standard Deviation 2.0	14.7 hour Standard Deviation 1.1	12.6 hour Standard Deviation 2.8	14.8 hour Standard Deviation 1.9	11.3 hour Standard Deviation 3.8

PRIMARY outcome

Timeframe: Up to day 3

Population: Patients who had PK samples collected and had CL/F data available were included in this analysis.

Plasma samples for pharmacokinetic (PK) analysis were drawn at pre-dose and at 0.5, 1, 2, 4, 8 (±1), 24 (±4) hours after the first dose of panobinostat, as well as prior to the second dose on Course 1 Day 3. Clearance (CL/F) was estimated using a noncompartmental method.

Outcome measures

Outcome measures
Measure	Stratum 1, Dose Level 1 (10 mg/m^2) n=10 Participants Recurrent or progressive DIPG patients received panobinostat orally every other day, 3 times per week at 10 mg/m\^2/day for three weeks on, one week off (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 1, Dose Level 2 (16 mg/m^2) n=5 Participants Recurrent or progressive DIPG patients received panobinostat orally every other day, 3 times per week at 16 mg/m\^2/day for three weeks on, one week off (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 1 (16 mg/m^2) n=3 Participants Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 16 mg/m\^2/day for every other week (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 2 (22 mg/m^2) n=7 Participants Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 22 mg/m\^2/day for every other week (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 3 (28 mg/m^2) n=7 Participants Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 28 mg/m\^2/day for every other week (1course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 4 (36 mg/m^2) n=4 Participants Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 36 mg/m\^2/day for every other week (1course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.
Clearance (CL/F)	87 L/h Standard Deviation 19	146 L/h Standard Deviation 104	156 L/h Standard Deviation 44	115 L/h Standard Deviation 34	93 L/h Standard Deviation 26	129 L/h Standard Deviation 109

PRIMARY outcome

Timeframe: Up to day 3

Population: Patients who had PK samples collected and had AUC data available were included.

Plasma samples for pharmacokinetic (PK) analysis were drawn at pre-dose and at 0.5, 1, 2, 4, 8 (±1), 24 (±4) hours after the first dose of panobinostat, as well as prior to the second dose on Course 1 Day 3. The area under the curve (AUC) was estimated using a noncompartmental method and calculated from time of dosing to the last measurable concentration.

Outcome measures

Outcome measures
Measure	Stratum 1, Dose Level 1 (10 mg/m^2) n=12 Participants Recurrent or progressive DIPG patients received panobinostat orally every other day, 3 times per week at 10 mg/m\^2/day for three weeks on, one week off (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 1, Dose Level 2 (16 mg/m^2) n=6 Participants Recurrent or progressive DIPG patients received panobinostat orally every other day, 3 times per week at 16 mg/m\^2/day for three weeks on, one week off (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 1 (16 mg/m^2) n=3 Participants Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 16 mg/m\^2/day for every other week (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 2 (22 mg/m^2) n=10 Participants Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 22 mg/m\^2/day for every other week (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 3 (28 mg/m^2) n=11 Participants Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 28 mg/m\^2/day for every other week (1course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 4 (36 mg/m^2) n=6 Participants Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 36 mg/m\^2/day for every other week (1course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.
Area Under the Curve (AUC)	102 h*ng/mL Standard Deviation 44	191 h*ng/mL Standard Deviation 146	143 h*ng/mL Standard Deviation 64	239 h*ng/mL Standard Deviation 71	284 h*ng/mL Standard Deviation 73	372 h*ng/mL Standard Deviation 222

SECONDARY outcome

Timeframe: From date on treatment until date of PD or death due to any cause or date of last follow-up

Population: Recurrent/progressive DIPG patients who were enrolled on stratum 1 and received at least one dose of panobinostat were included in the analysis. Per the associated protocol objective, all dose levels on stratum 1 were combined to estimate the PFS for this stratum.

PFS was measured from the time of treatment initiation until the time of progressive disease (PD) or death due to any cause for patients with an event, or until the time of last follow-up for patients who were progression free.

Outcome measures

Outcome measures
Measure	Stratum 1, Dose Level 1 (10 mg/m^2) n=19 Participants Recurrent or progressive DIPG patients received panobinostat orally every other day, 3 times per week at 10 mg/m\^2/day for three weeks on, one week off (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 1, Dose Level 2 (16 mg/m^2) Recurrent or progressive DIPG patients received panobinostat orally every other day, 3 times per week at 16 mg/m\^2/day for three weeks on, one week off (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 1 (16 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 16 mg/m\^2/day for every other week (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 2 (22 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 22 mg/m\^2/day for every other week (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 3 (28 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 28 mg/m\^2/day for every other week (1course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 4 (36 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 36 mg/m\^2/day for every other week (1course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.
Progression-free Survival (PFS) in Stratum 1	1.87 months Interval 0.73 to 9.0	—	—	—	—	—

SECONDARY outcome

Timeframe: From date on treatment until date of death due to any cause or date of last follow-up

OS was measured from the time of treatment initiation until the time of death due to any cause for patients who died, or until the time of last follow-up for patients who survived.

Outcome measures

Outcome measures
Measure	Stratum 1, Dose Level 1 (10 mg/m^2) n=19 Participants Recurrent or progressive DIPG patients received panobinostat orally every other day, 3 times per week at 10 mg/m\^2/day for three weeks on, one week off (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 1, Dose Level 2 (16 mg/m^2) Recurrent or progressive DIPG patients received panobinostat orally every other day, 3 times per week at 16 mg/m\^2/day for three weeks on, one week off (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 1 (16 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 16 mg/m\^2/day for every other week (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 2 (22 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 22 mg/m\^2/day for every other week (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 3 (28 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 28 mg/m\^2/day for every other week (1course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 4 (36 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 36 mg/m\^2/day for every other week (1course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.
Overall Survival (OS) in Stratum 1	5.23 months Interval 0.73 to 36.6	—	—	—	—	—

SECONDARY outcome

Timeframe: From date on treatment until date of PD or death due to any cause or date of last follow-up

Population: Non-progressed DIPG or H3K27M+ thalamic DMG patients who were enrolled on stratum 2 and received at least one dose of panobinostat were included in the analysis. Per the associated protocol objective, all dose levels on stratum 2 were combined to estimate the PFS for this stratum. Two patients who did not start protocol therapy were excluded.

Outcome measures

Outcome measures
Measure	Stratum 1, Dose Level 1 (10 mg/m^2) n=32 Participants Recurrent or progressive DIPG patients received panobinostat orally every other day, 3 times per week at 10 mg/m\^2/day for three weeks on, one week off (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 1, Dose Level 2 (16 mg/m^2) Recurrent or progressive DIPG patients received panobinostat orally every other day, 3 times per week at 16 mg/m\^2/day for three weeks on, one week off (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 1 (16 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 16 mg/m\^2/day for every other week (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 2 (22 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 22 mg/m\^2/day for every other week (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 3 (28 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 28 mg/m\^2/day for every other week (1course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 4 (36 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 36 mg/m\^2/day for every other week (1course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.
Progression-free Survival (PFS) in Stratum 2	3.83 months Interval 0.23 to 14.93	—	—	—	—	—

SECONDARY outcome

Timeframe: From date on treatment until date of death due to any cause or date of last follow-up

Population: Non-progressed DIPG or H3K27M+ thalamic DMG patients who were enrolled on stratum 2 and received at least one dose of panobinostat were included in the analysis. Per the associated protocol objective, all dose levels on stratum 2 were combined to estimate the OS for this stratum. Two patients who did not start protocol therapy were excluded.

OS was measured from the time of treatment initiation until the time of death due to any cause for patients who died, or until the time of last follow-up for patients who survived.

Outcome measures

Outcome measures
Measure	Stratum 1, Dose Level 1 (10 mg/m^2) n=32 Participants Recurrent or progressive DIPG patients received panobinostat orally every other day, 3 times per week at 10 mg/m\^2/day for three weeks on, one week off (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 1, Dose Level 2 (16 mg/m^2) Recurrent or progressive DIPG patients received panobinostat orally every other day, 3 times per week at 16 mg/m\^2/day for three weeks on, one week off (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 1 (16 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 16 mg/m\^2/day for every other week (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 2 (22 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 22 mg/m\^2/day for every other week (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 3 (28 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 28 mg/m\^2/day for every other week (1course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 4 (36 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 36 mg/m\^2/day for every other week (1course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.
Overall Survival (OS) in Stratum 2	9.13 months Interval 0.23 to 20.3	—	—	—	—	—

SECONDARY outcome

Timeframe: Blood samples were collected for cell-free DNA based assay at Course 1 Day 1 (C1D1), C2D1, C4D1, and C6D1.

Population: Only patients with cell-free DNA assay results available from blood samples were included in this analysis. Per the statistical section in the protocol, percentage of patients in whom the mutation was detected was summarized within each stratum and at each time point.

Cell-free DNA based assay was used to determine whether H3F3A K27M mutation could be detected in patients' blood samples. Percentage of patients in whom this mutation was detected was summarized within each stratum and at each time point.

Outcome measures

Outcome measures
Measure	Stratum 1, Dose Level 1 (10 mg/m^2) n=15 Participants Recurrent or progressive DIPG patients received panobinostat orally every other day, 3 times per week at 10 mg/m\^2/day for three weeks on, one week off (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 1, Dose Level 2 (16 mg/m^2) n=18 Participants Recurrent or progressive DIPG patients received panobinostat orally every other day, 3 times per week at 16 mg/m\^2/day for three weeks on, one week off (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 1 (16 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 16 mg/m\^2/day for every other week (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 2 (22 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 22 mg/m\^2/day for every other week (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 3 (28 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 28 mg/m\^2/day for every other week (1course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 4 (36 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 36 mg/m\^2/day for every other week (1course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.
Percentage of Patients With H3F3A K27M Mutation Detected in Blood Samples Course 1 Day 1	0 Percentage of participants	5.9 Percentage of participants	—	—	—	—
Percentage of Patients With H3F3A K27M Mutation Detected in Blood Samples Course 2 Day 1	0 Percentage of participants	23.1 Percentage of participants	—	—	—	—
Percentage of Patients With H3F3A K27M Mutation Detected in Blood Samples Course 4 Day 1	25.0 Percentage of participants	0 Percentage of participants	—	—	—	—
Percentage of Patients With H3F3A K27M Mutation Detected in Blood Samples Course 6 Day 1	—	20.0 Percentage of participants	—	—	—	—

SECONDARY outcome

Timeframe: Blood samples were collected for cell-free DNA based assay at Course 1 Day 1 (C1D1), C2D1, C4D1, and C6D1.

Cell-free DNA based assay was used to determine whether Hist1H3B K27M mutation could be detected in patients' blood samples. Percentage of patients in whom this mutation was detected was summarized within each stratum and at each time point.

Outcome measures

Outcome measures
Measure	Stratum 1, Dose Level 1 (10 mg/m^2) n=15 Participants Recurrent or progressive DIPG patients received panobinostat orally every other day, 3 times per week at 10 mg/m\^2/day for three weeks on, one week off (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 1, Dose Level 2 (16 mg/m^2) n=18 Participants Recurrent or progressive DIPG patients received panobinostat orally every other day, 3 times per week at 16 mg/m\^2/day for three weeks on, one week off (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 1 (16 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 16 mg/m\^2/day for every other week (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 2 (22 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 22 mg/m\^2/day for every other week (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 3 (28 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 28 mg/m\^2/day for every other week (1course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 4 (36 mg/m^2) Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 36 mg/m\^2/day for every other week (1course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.
Percentage of Patients With Hist1H3B K27M Mutation Detected in Blood Samples Course 1 Day 1	0 Percentage of participants	0 Percentage of participants	—	—	—	—
Percentage of Patients With Hist1H3B K27M Mutation Detected in Blood Samples Course 2 Day 1	0 Percentage of participants	0 Percentage of participants	—	—	—	—
Percentage of Patients With Hist1H3B K27M Mutation Detected in Blood Samples Course 4 Day 1	0 Percentage of participants	0 Percentage of participants	—	—	—	—
Percentage of Patients With Hist1H3B K27M Mutation Detected in Blood Samples Course 6 Day 1	—	0 Percentage of participants	—	—	—	—

SECONDARY outcome

Timeframe: Urine samples were collected for cell-free DNA based assay at Course 1 Day 1 (C1D1), C2D1, C4D1, and C6D1.

Per protocol, cell-free DNA based assay was to be used to determine whether H3F3A K27M mutation could be detected in patients' urine samples, and percentage of patients in whom this mutation was detected would be summarized within each stratum and at each time point. With current technologies available to the lab, no patients had cell-free DNA assay results from urine samples.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Urine samples were collected for cell-free DNA based assay at Course 1 Day 1 (C1D1), C2D1, C4D1, and C6D1.

Per protocol, cell-free DNA based assay was to be used to determine whether Hist1H3B K27M mutation could be detected in patients' urine samples, and percentage of patients in whom this mutation was detected would be summarized within each stratum and at each time point. With current technologies available to the lab, no patients had cell-free DNA assay results from urine samples.

Outcome measures

Outcome data not reported

Adverse Events

Stratum 1, Dose Level 1 (10 mg/m^2)

Serious events: 9 serious events

Other events: 13 other events

Deaths: 13 deaths

Stratum 1, Dose Level 2 (16 mg/m^2)

Serious events: 4 serious events

Other events: 6 other events

Deaths: 5 deaths

Stratum 2, Dose Level 1 (16 mg/m^2)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 3 deaths

Stratum 2, Dose Level 2 (22 mg/m^2)

Serious events: 5 serious events

Other events: 11 other events

Deaths: 5 deaths

Stratum 2, Dose Level 3 (28 mg/m^2)

Serious events: 4 serious events

Other events: 12 other events

Deaths: 11 deaths

Stratum 2, Dose Level 4 (36 mg/m^2)

Serious events: 4 serious events

Other events: 6 other events

Deaths: 5 deaths

Serious adverse events

Serious adverse events
Measure	Stratum 1, Dose Level 1 (10 mg/m^2) n=13 participants at risk Recurrent or progressive DIPG patients received panobinostat orally every other day, 3 times per week at 10 mg/m\^2/day for three weeks on, one week off (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 1, Dose Level 2 (16 mg/m^2) n=6 participants at risk Recurrent or progressive DIPG patients received panobinostat orally every other day, 3 times per week at 16 mg/m\^2/day for three weeks on, one week off (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 1 (16 mg/m^2) n=3 participants at risk Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 16 mg/m\^2/day for every other week (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 2 (22 mg/m^2) n=11 participants at risk Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 22 mg/m\^2/day for every other week (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 3 (28 mg/m^2) n=12 participants at risk Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 28 mg/m\^2/day for every other week (1course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 4 (36 mg/m^2) n=6 participants at risk Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 36 mg/m\^2/day for every other week (1course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.
Gastrointestinal disorders Abdominal pain	7.7% 1/13 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Gastrointestinal disorders Dysphagia	7.7% 1/13 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Gastrointestinal disorders Vomiting	7.7% 1/13 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
General disorders Fatigue	7.7% 1/13 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
General disorders Gait disturbance	7.7% 1/13 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Infections and infestations Catheter related infection	7.7% 1/13 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Infections and infestations Sepsis	7.7% 1/13 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Infections and infestations Urinary tract infection	7.7% 1/13 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Investigations Neutrophil count decreased	0.00% 0/13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	33.3% 2/6 • Number of events 3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	9.1% 1/11 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 2/12 • Number of events 4 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Investigations Platelet count decreased	0.00% 0/13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	33.3% 2/6 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	9.1% 1/11 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	8.3% 1/12 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Investigations White blood cell decreased	0.00% 0/13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	7.7% 1/13 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	9.1% 1/11 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Musculoskeletal and connective tissue disorders Muscle weakness left-sided	0.00% 0/13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Musculoskeletal and connective tissue disorders Muscle weakness right-sided	7.7% 1/13 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Musculoskeletal and connective tissue disorders Trismus	0.00% 0/13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	9.1% 1/11 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - other, specify	46.2% 6/13 • Number of events 8 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Nervous system disorders Ataxia	7.7% 1/13 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Nervous system disorders Depressed level of consciousness	15.4% 2/13 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	9.1% 1/11 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Nervous system disorders Dizziness	0.00% 0/13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Nervous system disorders Dysarthria	7.7% 1/13 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Nervous system disorders Facial muscle weakness	7.7% 1/13 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Nervous system disorders Headache	7.7% 1/13 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Nervous system disorders Hydrocephalus	7.7% 1/13 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	18.2% 2/11 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	8.3% 1/12 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Nervous system disorders Nervous system disorders - other, specify	15.4% 2/13 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Nervous system disorders Reversible posterior leukoencephalopathy syndrome	0.00% 0/13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	9.1% 1/11 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Renal and urinary disorders Hematuria	7.7% 1/13 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Respiratory, thoracic and mediastinal disorders Apnea	7.7% 1/13 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Respiratory, thoracic and mediastinal disorders Dyspnea	7.7% 1/13 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Respiratory, thoracic and mediastinal disorders Respiratory failure	23.1% 3/13 • Number of events 3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - other, specify	0.00% 0/13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	8.3% 1/12 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Vascular disorders Hypertension	7.7% 1/13 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	18.2% 2/11 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.

Other adverse events

Other adverse events
Measure	Stratum 1, Dose Level 1 (10 mg/m^2) n=13 participants at risk Recurrent or progressive DIPG patients received panobinostat orally every other day, 3 times per week at 10 mg/m\^2/day for three weeks on, one week off (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 1, Dose Level 2 (16 mg/m^2) n=6 participants at risk Recurrent or progressive DIPG patients received panobinostat orally every other day, 3 times per week at 16 mg/m\^2/day for three weeks on, one week off (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 1 (16 mg/m^2) n=3 participants at risk Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 16 mg/m\^2/day for every other week (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 2 (22 mg/m^2) n=11 participants at risk Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 22 mg/m\^2/day for every other week (1 course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 3 (28 mg/m^2) n=12 participants at risk Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 28 mg/m\^2/day for every other week (1course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.	Stratum 2, Dose Level 4 (36 mg/m^2) n=6 participants at risk Non-progressed DIPG or H3K27M+ thalamic DMG patients received panobinostat orally every other day, 3 times per week at 36 mg/m\^2/day for every other week (1course = 28 days) for up to 26 courses in the absence of disease progression or unacceptable toxicity.
Investigations Aspartate aminotransferase increased	30.8% 4/13 • Number of events 5 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	50.0% 3/6 • Number of events 4 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	36.4% 4/11 • Number of events 4 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 2/12 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	33.3% 2/6 • Number of events 3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Blood and lymphatic system disorders Anemia	23.1% 3/13 • Number of events 3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	27.3% 3/11 • Number of events 6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	58.3% 7/12 • Number of events 16 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	50.0% 3/6 • Number of events 7 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Cardiac disorders Cardiac disorders - other, specify	0.00% 0/13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	8.3% 1/12 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Cardiac disorders Right ventricular dysfunction	0.00% 0/13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Cardiac disorders Sinus bradycardia	7.7% 1/13 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	8.3% 1/12 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Cardiac disorders Sinus tachycardia	7.7% 1/13 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	9.1% 1/11 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	8.3% 1/12 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Eye disorders Extraocular muscle paresis	7.7% 1/13 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Gastrointestinal disorders Abdominal pain	7.7% 1/13 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	33.3% 1/3 • Number of events 3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	18.2% 2/11 • Number of events 3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	8.3% 1/12 • Number of events 4 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Gastrointestinal disorders Constipation	7.7% 1/13 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	33.3% 1/3 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	9.1% 1/11 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	50.0% 3/6 • Number of events 3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Gastrointestinal disorders Diarrhea	15.4% 2/13 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	50.0% 3/6 • Number of events 3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	33.3% 1/3 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	72.7% 8/11 • Number of events 13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	75.0% 9/12 • Number of events 15 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	66.7% 4/6 • Number of events 6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Gastrointestinal disorders Dysphagia	7.7% 1/13 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	8.3% 1/12 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Gastrointestinal disorders Gastroesophageal reflux disease	7.7% 1/13 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Gastrointestinal disorders Gastrointestinal disorders - other, specify	0.00% 0/13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	66.7% 2/3 • Number of events 3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	9.1% 1/11 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	8.3% 1/12 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Gastrointestinal disorders Mucositis oral	0.00% 0/13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Gastrointestinal disorders Nausea	7.7% 1/13 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	66.7% 4/6 • Number of events 5 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	100.0% 3/3 • Number of events 11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	45.5% 5/11 • Number of events 7 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	58.3% 7/12 • Number of events 11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	33.3% 2/6 • Number of events 4 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Gastrointestinal disorders Vomiting	15.4% 2/13 • Number of events 4 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	33.3% 2/6 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	66.7% 2/3 • Number of events 8 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	72.7% 8/11 • Number of events 21 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	66.7% 8/12 • Number of events 23 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	83.3% 5/6 • Number of events 7 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
General disorders Fatigue	38.5% 5/13 • Number of events 7 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	50.0% 3/6 • Number of events 3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	66.7% 2/3 • Number of events 3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	45.5% 5/11 • Number of events 7 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	41.7% 5/12 • Number of events 6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	50.0% 3/6 • Number of events 3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
General disorders Fever	0.00% 0/13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	9.1% 1/11 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
General disorders Gait disturbance	7.7% 1/13 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
General disorders Irritability	0.00% 0/13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
General disorders Malaise	7.7% 1/13 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Infections and infestations Catheter related infection	7.7% 1/13 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Infections and infestations Infections and infestations - other, specify	0.00% 0/13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	8.3% 1/12 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Infections and infestations Mucosal infection	7.7% 1/13 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Infections and infestations Paronychia	0.00% 0/13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	8.3% 1/12 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Infections and infestations Skin infection	0.00% 0/13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Infections and infestations Vaginal infection	0.00% 0/13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Injury, poisoning and procedural complications Bruising	0.00% 0/13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	9.1% 1/11 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Investigations Alanine aminotransferase increased	61.5% 8/13 • Number of events 10 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	33.3% 2/6 • Number of events 3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	36.4% 4/11 • Number of events 4 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	8.3% 1/12 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	33.3% 2/6 • Number of events 5 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Investigations Alkaline phosphatase increased	15.4% 2/13 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Investigations Blood bilirubin increased	7.7% 1/13 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	9.1% 1/11 • Number of events 4 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 2/12 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	33.3% 2/6 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Investigations Creatinine increased	0.00% 0/13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	18.2% 2/11 • Number of events 3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 2/12 • Number of events 3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	33.3% 2/6 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Investigations Electrocardiogram qt corrected interval prolonged	0.00% 0/13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	9.1% 1/11 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	33.3% 2/6 • Number of events 4 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Investigations Hemoglobin increased	23.1% 3/13 • Number of events 5 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Investigations Investigations - other, specify	23.1% 3/13 • Number of events 3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	33.3% 1/3 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	8.3% 1/12 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	33.3% 2/6 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Investigations Lymphocyte count decreased	53.8% 7/13 • Number of events 17 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	100.0% 6/6 • Number of events 7 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	72.7% 8/11 • Number of events 22 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	83.3% 10/12 • Number of events 30 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	66.7% 4/6 • Number of events 19 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Investigations Neutrophil count decreased	15.4% 2/13 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	50.0% 3/6 • Number of events 4 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	66.7% 2/3 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	45.5% 5/11 • Number of events 13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	58.3% 7/12 • Number of events 30 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	100.0% 6/6 • Number of events 18 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Investigations Platelet count decreased	76.9% 10/13 • Number of events 14 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	83.3% 5/6 • Number of events 6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	100.0% 3/3 • Number of events 6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	90.9% 10/11 • Number of events 21 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	91.7% 11/12 • Number of events 24 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	66.7% 4/6 • Number of events 8 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Investigations Weight loss	0.00% 0/13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	66.7% 2/3 • Number of events 5 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	18.2% 2/11 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	25.0% 3/12 • Number of events 4 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Investigations White blood cell decreased	30.8% 4/13 • Number of events 4 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	83.3% 5/6 • Number of events 5 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	66.7% 2/3 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	72.7% 8/11 • Number of events 24 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	91.7% 11/12 • Number of events 46 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	83.3% 5/6 • Number of events 18 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Metabolism and nutrition disorders Anorexia	15.4% 2/13 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	66.7% 2/3 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	27.3% 3/11 • Number of events 3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 2/12 • Number of events 3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	33.3% 2/6 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Metabolism and nutrition disorders Dehydration	0.00% 0/13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	8.3% 1/12 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	33.3% 2/6 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Metabolism and nutrition disorders Hyperglycemia	15.4% 2/13 • Number of events 5 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	9.1% 1/11 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	8.3% 1/12 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Metabolism and nutrition disorders Hypermagnesemia	7.7% 1/13 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	9.1% 1/11 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	25.0% 3/12 • Number of events 3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Metabolism and nutrition disorders Hypernatremia	0.00% 0/13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	9.1% 1/11 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Metabolism and nutrition disorders Hypoalbuminemia	46.2% 6/13 • Number of events 8 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	27.3% 3/11 • Number of events 3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	8.3% 1/12 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Metabolism and nutrition disorders Hypocalcemia	15.4% 2/13 • Number of events 5 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	18.2% 2/11 • Number of events 3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	8.3% 1/12 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Metabolism and nutrition disorders Hypoglycemia	23.1% 3/13 • Number of events 3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	9.1% 1/11 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	8.3% 1/12 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Metabolism and nutrition disorders Hypokalemia	15.4% 2/13 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	33.3% 2/6 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	18.2% 2/11 • Number of events 3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	25.0% 3/12 • Number of events 4 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Metabolism and nutrition disorders Hypomagnesemia	7.7% 1/13 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Metabolism and nutrition disorders Hyponatremia	7.7% 1/13 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	9.1% 1/11 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Metabolism and nutrition disorders Hypophosphatemia	15.4% 2/13 • Number of events 3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	33.3% 2/6 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	54.5% 6/11 • Number of events 6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	41.7% 5/12 • Number of events 6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	33.3% 2/6 • Number of events 3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Metabolism and nutrition disorders Metabolism and nutrition disorders - other, specify	23.1% 3/13 • Number of events 5 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	9.1% 1/11 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Musculoskeletal and connective tissue disorders Back pain	7.7% 1/13 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	15.4% 2/13 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Musculoskeletal and connective tissue disorders Muscle weakness left-sided	0.00% 0/13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	8.3% 1/12 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - other, specify	15.4% 2/13 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Nervous system disorders Ataxia	0.00% 0/13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	33.3% 2/6 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	9.1% 1/11 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	8.3% 1/12 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Nervous system disorders Dizziness	0.00% 0/13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	33.3% 1/3 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	9.1% 1/11 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Nervous system disorders Dysarthria	0.00% 0/13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Nervous system disorders Dysgeusia	0.00% 0/13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	33.3% 1/3 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	8.3% 1/12 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Nervous system disorders Headache	7.7% 1/13 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	33.3% 1/3 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	9.1% 1/11 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 2/12 • Number of events 3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Nervous system disorders Intracranial hemorrhage	0.00% 0/13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	8.3% 1/12 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Psychiatric disorders Insomnia	15.4% 2/13 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Renal and urinary disorders Renal and urinary disorders - other, specify	7.7% 1/13 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Renal and urinary disorders Urinary incontinence	0.00% 0/13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	8.3% 1/12 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Respiratory, thoracic and mediastinal disorders Cough	7.7% 1/13 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Respiratory, thoracic and mediastinal disorders Dyspnea	15.4% 2/13 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	9.1% 1/11 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	9.1% 1/11 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Respiratory, thoracic and mediastinal disorders Productive cough	7.7% 1/13 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - other, specify	0.00% 0/13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Skin and subcutaneous tissue disorders Alopecia	7.7% 1/13 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Skin and subcutaneous tissue disorders Dry skin	7.7% 1/13 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Skin and subcutaneous tissue disorders Rash acneiform	7.7% 1/13 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	9.1% 1/11 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	16.7% 1/6 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	9.1% 1/11 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - other, specify	15.4% 2/13 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Vascular disorders Flushing	0.00% 0/13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	33.3% 1/3 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/11 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Vascular disorders Hypertension	30.8% 4/13 • Number of events 5 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	18.2% 2/11 • Number of events 2 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	8.3% 1/12 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.
Vascular disorders Superficial thrombophlebitis	0.00% 0/13 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/3 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	9.1% 1/11 • Number of events 1 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/12 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.	0.00% 0/6 • Approximately 2 years after initiation of protocol treatment Adverse events (AEs) were graded using CTCAE v4.0. AEs collected per protocol included a) grade 1 or 2 AEs if attribution was at least possibly related to panobinostat, and b) all grade 3+ AEs on treatment and within 30 days off treatment. All these AEs were summarized in SAE and Other AE tables below. All mortalities on this study were due to disease, except one for upper airway obstruction. Two patients on stratum 2 did not start protocol therapy and were not counted as at risk.

Additional Information

Dr. Arzu Onar-Thomas

St. Jude Children's Research Hospital

Phone: 901-595-5499

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place