Trial Outcomes & Findings for Phase II Study Incorporating Pegylated Interferon In the Treatment For Children With High-Risk Melanoma (NCT NCT00539591)

NCT ID: NCT00539591

Last Updated: 2025-12-23

Results Overview

Tumor response rate of stratum B1 participants was evaluated after 1 treatment course of temozolomide plus peginterferon ɑ-2b. Complete response (CR) and partial response (PR) confirmed with repeated scan at least 4 weeks apart following completion of course 1 therapy. CR defined as disappearance of all target and non-target lesions with no new lesions detected. If available, no disease must be detected by immunocytology or serum tumor markers. PR defined as at least 30% decrease in disease measurement compared to disease measurement at study entry with no new lesions detected. Progressive disease (PD) defined as at least 20% increase in the disease measurement compared to the smallest disease measurement recorded since start of treatment, or appearance of one or more new lesions. Stable disease defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD compared to smallest disease measurement since start of treatment.

• Recruitment status: ACTIVE_NOT_RECRUITING
• Study phase: PHASE2
• Target enrollment: 29 participants
• Primary outcome timeframe: 8 weeks
• Results posted on: 2025-12-23

Participant Flow

A total of 29 patients were enrolled between May 9, 2008 and August 22, 2012. Of the 29 participants, 21 were enrolled at St. Jude Children's Research Hospital (SJCRH), 7 at MD Anderson, and 1 at Rady Children's Hospital. Twenty-three participants met stratum A eligibility, 2 met stratum B1 eligibility and 4 met stratum B2 eligibility.

Participant milestones

Measure	Peginterferon ɑ-2b/Non-pegylated Interferon ɑ-2b Stratum A: American Joint Committee on Cancer (AJCC) resected Stages IIC, IIIA, and IIIB Participants received recombinant interferon ɑ-2b 20 million units/m\^2/day intravenously 5 consecutive days per week for 4 weeks followed by peginterferon ɑ-2b 1 mcg/kg subcutaneously once a week for 48 weeks.	Temozolomide/Peginterferon ɑ-2b With Measureable Disease Stratum B1: American Joint Committee on Cancer (AJCC) resected Stage IIIC, unresectable Stage III, Stage IV, and recurrent participants with measurable disease Participants received 8 weekly doses of peginterferon ɑ-2b 0.5 mcg/kg/dose subcutaneously in combination with temozolomide 75 mg/m\^2/dose by mouth daily for 6 weeks followed by 2 week break. The duration of each treatment course was 8 weeks.	Temozolomide/Peginterferon ɑ-2b Without Measureable Disease Stratum B2: American Joint Committee on Cancer (AJCC) resected Stage IIIC, unresectable Stage III, Stage IV, and recurrent participants without measurable disease Participants received 8 weekly doses of peginterferon ɑ-2b 0.5 mcg/kg/dose subcutaneously in combination with temozolomide 75 mg/m\^2/dose by mouth daily for 6 weeks followed by 2 week break. The duration of each treatment course was 8 weeks. Stratum B2 (no measurable disease) proceeded with 7 courses as outlined.
Overall Study STARTED	23	2	4
Overall Study COMPLETED	18	0	1
Overall Study NOT COMPLETED	5	2	3

Reasons for withdrawal

Measure	Peginterferon ɑ-2b/Non-pegylated Interferon ɑ-2b Stratum A: American Joint Committee on Cancer (AJCC) resected Stages IIC, IIIA, and IIIB Participants received recombinant interferon ɑ-2b 20 million units/m\^2/day intravenously 5 consecutive days per week for 4 weeks followed by peginterferon ɑ-2b 1 mcg/kg subcutaneously once a week for 48 weeks.	Temozolomide/Peginterferon ɑ-2b With Measureable Disease Stratum B1: American Joint Committee on Cancer (AJCC) resected Stage IIIC, unresectable Stage III, Stage IV, and recurrent participants with measurable disease Participants received 8 weekly doses of peginterferon ɑ-2b 0.5 mcg/kg/dose subcutaneously in combination with temozolomide 75 mg/m\^2/dose by mouth daily for 6 weeks followed by 2 week break. The duration of each treatment course was 8 weeks.	Temozolomide/Peginterferon ɑ-2b Without Measureable Disease Stratum B2: American Joint Committee on Cancer (AJCC) resected Stage IIIC, unresectable Stage III, Stage IV, and recurrent participants without measurable disease Participants received 8 weekly doses of peginterferon ɑ-2b 0.5 mcg/kg/dose subcutaneously in combination with temozolomide 75 mg/m\^2/dose by mouth daily for 6 weeks followed by 2 week break. The duration of each treatment course was 8 weeks. Stratum B2 (no measurable disease) proceeded with 7 courses as outlined.
Overall Study Toxicity	3	0	0
Overall Study Disease progression	2	2	3

Baseline Characteristics

Phase II Study Incorporating Pegylated Interferon In the Treatment For Children With High-Risk Melanoma

Baseline characteristics by cohort

Measure	Peginterferon ɑ-2b/Non-pegylated Interferon ɑ-2b n=23 Participants Stratum A: American Joint Committee on Cancer (AJCC) resected Stages IIC, IIIA, and IIIB Participants received recombinant interferon ɑ-2b 20 million units/m\^2/day intravenously 5 consecutive days per week for 4 weeks followed by peginterferon ɑ-2b 1 mcg/kg subcutaneously once a week for 48 weeks.	Temozolomide/Peginterferon ɑ-2b With Measureable Disease n=2 Participants Stratum B1: American Joint Committee on Cancer (AJCC) resected Stage IIIC, unresectable Stage III, Stage IV, and recurrent participants with measurable disease Participants received 8 weekly doses of peginterferon ɑ-2b 0.5 mcg/kg/dose subcutaneously in combination with temozolomide 75 mg/m\^2/dose by mouth daily for 6 weeks followed by 2 week break. The duration of each treatment course was 8 weeks.	Temozolomide/Peginterferon ɑ-2b Without Measureable Disease n=4 Participants Stratum B2: American Joint Committee on Cancer (AJCC) resected Stage IIIC, unresectable Stage III, Stage IV, and recurrent participants without measurable disease Participants received 8 weekly doses of peginterferon ɑ-2b 0.5 mcg/kg/dose subcutaneously in combination with temozolomide 75 mg/m\^2/dose by mouth daily for 6 weeks followed by 2 week break. The duration of each treatment course was 8 weeks. Stratum B2 (no measurable disease) proceeded with 7 courses as outlined.	Total n=29 Participants Total of all reporting groups
Age, Continuous	10.3 years FULL_RANGE 2.4 • n=68 Participants	11.9 years FULL_RANGE 3.96 • n=4 Participants	18.4 years FULL_RANGE 3.6 • n=219 Participants	10.77 years FULL_RANGE 2.4 • n=219 Participants
Sex: Female, Male Female	15 Participants n=68 Participants	0 Participants n=4 Participants	1 Participants n=219 Participants	16 Participants n=219 Participants
Sex: Female, Male Male	8 Participants n=68 Participants	2 Participants n=4 Participants	3 Participants n=219 Participants	13 Participants n=219 Participants

PRIMARY outcome

Timeframe: 8 weeks

Tumor response rate of stratum B1 participants was evaluated after 1 treatment course of temozolomide plus peginterferon ɑ-2b. Complete response (CR) and partial response (PR) confirmed with repeated scan at least 4 weeks apart following completion of course 1 therapy. CR defined as disappearance of all target and non-target lesions with no new lesions detected. If available, no disease must be detected by immunocytology or serum tumor markers. PR defined as at least 30% decrease in disease measurement compared to disease measurement at study entry with no new lesions detected. Progressive disease (PD) defined as at least 20% increase in the disease measurement compared to the smallest disease measurement recorded since start of treatment, or appearance of one or more new lesions. Stable disease defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD compared to smallest disease measurement since start of treatment.

Outcome measures

Measure	End of Therapy QoL assessment completed at end of therapy.	6 Months After End of Therapy QoL assessment completed 6 months after end of therapy.	12 Months After End of Therapy QoL assessment completed 12 months after end of therapy.	Week 2 n=2 Participants QoL assessment completed at Week 2.	Week 4 QoL assessment completed at Week 4.	Week 8 QoL assessment completed at Week 8.	Week 12 QoL assessment completed at Week 12.	Week 24 QoL assessment completed at Week 24.	End of Therapy QoL assessment completed at end of therapy.
Tumor Response Rate Progressive Disease	—	—	—	2 participants	—	—	—	—	—
Tumor Response Rate Clinical Remission	—	—	—	0 participants	—	—	—	—	—

PRIMARY outcome

Timeframe: 52 weeks

Population: This toxicity report was based on intention to treat population (ITT), all patients enrolled were included. The study did not meet its accrual goals within the planned timeframe due to slow accrual.

The objective was to assess the safety of temozolomide administered in combination with peginterferon a-2b in Stratum B participants.

Accrual was suspended any time during therapy if 2 or more of 6, 4 or more of 12, 6 or more of 18, 8 or more of 24, 10 or more of 30 participants experienced target toxicity defined as:

• Grade 4 non-hematologic (non-hem) toxicity that does not resolve to ≤grade 1 within 2 weeks from the time next dose is due and is determined to be probably or definitely related to protocol therapy
• Grade 4 non-hem toxicity that is NOT constitutional symptoms (fever, chills, fatigue and/or pain)
• Grade 3 elevations in creatinine or BUN that are determined to be probably or definitely related to protocol therapy
• Grade 4 cardiopulmonary toxicity that is determined to be probably or definitely related to protocol therapy
• Grade 4 mood alteration (suicidal ideation; danger to self or others)

Outcome measures

Measure	End of Therapy QoL assessment completed at end of therapy.	6 Months After End of Therapy QoL assessment completed 6 months after end of therapy.	12 Months After End of Therapy QoL assessment completed 12 months after end of therapy.	Week 2 n=2 Participants QoL assessment completed at Week 2.	Week 4 n=4 Participants QoL assessment completed at Week 4.	Week 8 QoL assessment completed at Week 8.	Week 12 QoL assessment completed at Week 12.	Week 24 QoL assessment completed at Week 24.	End of Therapy QoL assessment completed at end of therapy.
Number of Patients Who Experience Toxicity at or Above the Target Toxicity for Strata B1 and B2	—	—	—	0 participants	0 participants	—	—	—	—

PRIMARY outcome

Timeframe: 52 weeks

Population: Number of participants for the analysis was based on the intent to treat population, all patients enrolled were included. Participants were enrolled on Stratum A until the accrual goals were met on Stratum B.

The objective was to study the feasibility and safety of administering peginterferon a-2b weekly for 48 weeks following the initial induction phase to Stratum A participants.

Accrual was suspended during the 48-week course if 2 or more of 6, 4 or more of 12, 6 or more of 18, 8 or more of 24, 10 or more of 30 participants experienced target toxicity defined as:

• Grade 4 non-hematologic (non-hem) toxicity that does not resolve to ≤grade 1 within 2 weeks from the time next dose is due and is determined to be probably or definitely related to protocol therapy
• Grade 4 non-hem toxicity that is NOT constitutional symptoms (fever, chills, fatigue and/or pain)
• Grade 3 elevations in creatinine or BUN that are determined to be probably or definitely related to protocol therapy
• Grade 4 cardiopulmonary toxicity that is determined to be probably or definitely related to protocol therapy
• Grade 4 mood alteration (suicidal ideation; danger to self or others)

Outcome measures

Measure	End of Therapy QoL assessment completed at end of therapy.	6 Months After End of Therapy QoL assessment completed 6 months after end of therapy.	12 Months After End of Therapy QoL assessment completed 12 months after end of therapy.	Week 2 n=23 Participants QoL assessment completed at Week 2.	Week 4 QoL assessment completed at Week 4.	Week 8 QoL assessment completed at Week 8.	Week 12 QoL assessment completed at Week 12.	Week 24 QoL assessment completed at Week 24.	End of Therapy QoL assessment completed at end of therapy.
Number of Patients Who Experience Toxicity at or Above the Target Toxicity for Stratum A Patients Grade 4 non-hem toxicity	—	—	—	2 participants	—	—	—	—	—
Number of Patients Who Experience Toxicity at or Above the Target Toxicity for Stratum A Patients Grade 4 non-hem/NOT constitutional	—	—	—	0 participants	—	—	—	—	—
Number of Patients Who Experience Toxicity at or Above the Target Toxicity for Stratum A Patients Grade 3 elevations in creatinine or BUN	—	—	—	0 participants	—	—	—	—	—
Number of Patients Who Experience Toxicity at or Above the Target Toxicity for Stratum A Patients Grade 4 cardiopulmonary toxicity	—	—	—	0 participants	—	—	—	—	—
Number of Patients Who Experience Toxicity at or Above the Target Toxicity for Stratum A Patients Grade 4 mood alteration	—	—	—	1 participants	—	—	—	—	—

PRIMARY outcome

Timeframe: 3 years from diagnosis

The probability of EFS was estimated as time to first event (relapse, death or second malignancy). As of April 2016, 21 out of 23 participants had no events. The EFS rate was estimated by Kaplan-Meier method.

Outcome measures

Measure	End of Therapy QoL assessment completed at end of therapy.	6 Months After End of Therapy QoL assessment completed 6 months after end of therapy.	12 Months After End of Therapy QoL assessment completed 12 months after end of therapy.	Week 2 n=23 Participants QoL assessment completed at Week 2.	Week 4 QoL assessment completed at Week 4.	Week 8 QoL assessment completed at Week 8.	Week 12 QoL assessment completed at Week 12.	Week 24 QoL assessment completed at Week 24.	End of Therapy QoL assessment completed at end of therapy.
Probability of Event-free Survival (EFS) of Stratum A Participants	—	—	—	0.913 probability Interval 0.79 to 1.0	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Before first dose, and 24, 96 and 168 hours after dose during weeks 5 and 28

Population: Only one patient had evaluable data in Stratum B and is not included in the final analysis, because data from more than one patient are required for nonlinear-mixed effects modeling.

The pharmacokinetic (PK) analysis of pegylated ɑ-2b included only patients within Stratum A who had PK studies performed.

Samples were analyzed for pegylated interferon ɑ-2b concentrations by using the VeriKine Human Interferon Alpha ELISA Kit following the manufacturer's instructions, and concentration-time data were analyzed by nonlinear-mixed effects modeling as implemented in NONMEM.

Outcome measures

Measure	End of Therapy QoL assessment completed at end of therapy.	6 Months After End of Therapy QoL assessment completed 6 months after end of therapy.	12 Months After End of Therapy QoL assessment completed 12 months after end of therapy.	Week 2 n=16 Participants QoL assessment completed at Week 2.	Week 4 QoL assessment completed at Week 4.	Week 8 QoL assessment completed at Week 8.	Week 12 QoL assessment completed at Week 12.	Week 24 QoL assessment completed at Week 24.	End of Therapy QoL assessment completed at end of therapy.
Median Steady State Trough Concentration of Pegylated Interferon ɑ-2B	—	—	—	52.8 pcg/ml Interval 13.8 to 152.4	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Before first dose, and 24, 96 and 168 hours after dose during weeks 5 and 28

Population: Only one Stratum B patient had evaluable data and is not included in final analysis, because data from more than one patient are required for nonlinear-mixed effects modeling. Two patients in Week 5 and three in Week 28 were excluded due to inadequate sampling to characterize an AUC value.

Pharmacokinetic (PK) analysis of pegylated ɑ-2b included only Stratum A patients who had PK studies performed.

Samples were analyzed for pegylated interferon ɑ-2b concentrations by using the VeriKine Human Interferon Alpha ELISA Kit following the manufacturer's instructions, and concentration-time data were analyzed by nonlinear-mixed effects modeling as implemented in NONMEM. AUC is given as Time 0 through infinity.

Outcome measures

Measure	End of Therapy QoL assessment completed at end of therapy.	6 Months After End of Therapy QoL assessment completed 6 months after end of therapy.	12 Months After End of Therapy QoL assessment completed 12 months after end of therapy.	Week 2 n=7 Participants QoL assessment completed at Week 2.	Week 4 n=6 Participants QoL assessment completed at Week 4.	Week 8 QoL assessment completed at Week 8.	Week 12 QoL assessment completed at Week 12.	Week 24 QoL assessment completed at Week 24.	End of Therapy QoL assessment completed at end of therapy.
Area Under the Curve (AUC) of Pegylated Interferon ɑ-2B	—	—	—	50556 pcg * hr/ml Interval 36166.0 to 58980.0	48480 pcg * hr/ml Interval 34024.0 to 59857.0	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Before first dose, and 24, 96 and 168 hours after dose during weeks 5 and 28

Population: Only one Stratum B patient had evaluable data and is not included in final analysis, because data from more than one patient are required for nonlinear-mixed effects modeling. Two patients in Week 5 and three in Week 28 were excluded due to inadequate sampling to characterize an AUC value.

Pharmacokinetic (PK) analysis of pegylated ɑ-2b included only Stratum A patients who had PK studies performed.

Samples were analyzed for pegylated interferon ɑ-2b concentrations by using the VeriKine Human Interferon Alpha ELISA Kit following the manufacturer's instructions, and concentration-time data were analyzed by nonlinear-mixed effects modeling as implemented in NONMEM.

Outcome measures

Measure	End of Therapy QoL assessment completed at end of therapy.	6 Months After End of Therapy QoL assessment completed 6 months after end of therapy.	12 Months After End of Therapy QoL assessment completed 12 months after end of therapy.	Week 2 n=9 Participants QoL assessment completed at Week 2.	Week 4 QoL assessment completed at Week 4.	Week 8 QoL assessment completed at Week 8.	Week 12 QoL assessment completed at Week 12.	Week 24 QoL assessment completed at Week 24.	End of Therapy QoL assessment completed at end of therapy.
ɑ Half Life of Pegylated Interferon ɑ-2B	—	—	—	24.8 hours Interval 16.6 to 40.6	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Before first dose, and 24, 96 and 168 hours after dose during weeks 5 and 28

Population: Only one Stratum B patient had evaluable data and is not included in final analysis, because data from more than one patient are required for nonlinear-mixed effects modeling due to differences in clinical variables. Two patients in Week 5 and three in Week 28 were excluded due to inadequate sampling to characterize an AUC value.

Pharmacokinetic (PK) analysis of pegylated ɑ-2b included only Stratum A patients who had PK studies performed.

Samples were analyzed for pegylated interferon ɑ-2b concentrations by using the VeriKine Human Interferon Alpha ELISA Kit following the manufacturer's instructions, and concentration-time data were analyzed by nonlinear-mixed effects modeling as implemented in NONMEM.

Outcome measures

Measure	End of Therapy QoL assessment completed at end of therapy.	6 Months After End of Therapy QoL assessment completed 6 months after end of therapy.	12 Months After End of Therapy QoL assessment completed 12 months after end of therapy.	Week 2 n=9 Participants QoL assessment completed at Week 2.	Week 4 QoL assessment completed at Week 4.	Week 8 QoL assessment completed at Week 8.	Week 12 QoL assessment completed at Week 12.	Week 24 QoL assessment completed at Week 24.	End of Therapy QoL assessment completed at end of therapy.
Volume of Central Compartment (Vc) of Pegylated Interferon ɑ-2B	—	—	—	772 ml/kg Interval 594.0 to 1410.0	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Before first dose, and 24, 96 and 168 hours after dose during weeks 5 and 28

Population: Only one Stratum B patient had evaluable data and is not included in final analysis due to differences in clinical variables, because data from more than one patient are required for nonlinear-mixed effects modeling. Two patients in Week 5 and three in Week 28 were excluded due to inadequate sampling to characterize an AUC value.

Pharmacokinetic (PK) analysis of pegylated ɑ-2b included only Stratum A patients who had PK studies performed.

Samples were analyzed for pegylated interferon ɑ-2b concentrations by using the VeriKine Human Interferon Alpha ELISA Kit following the manufacturer's instructions, and concentration-time data were analyzed by nonlinear-mixed effects modeling as implemented in NONMEM.

Outcome measures

Measure	End of Therapy QoL assessment completed at end of therapy.	6 Months After End of Therapy QoL assessment completed 6 months after end of therapy.	12 Months After End of Therapy QoL assessment completed 12 months after end of therapy.	Week 2 n=9 Participants QoL assessment completed at Week 2.	Week 4 QoL assessment completed at Week 4.	Week 8 QoL assessment completed at Week 8.	Week 12 QoL assessment completed at Week 12.	Week 24 QoL assessment completed at Week 24.	End of Therapy QoL assessment completed at end of therapy.
Apparent Clearance (CL) of Pegylated Interferon ɑ-2B	—	—	—	19.8 ml/hr/kg Interval 16.7 to 31.4	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Before first dose, and 1, 2, 4, 6, 8, 12, and 24 hours postinfusion

Population: The pharmacokinetic(PK) analysis of pegylated ɑ-2b included only patients within Stratum A who had PK studies performed. Only one patient had evaluable data in Stratum B and is not included in the final analysis due to differences in clinical variables.

Samples were analyzed for interferon ɑ-2b concentrations by using the VeriKine Human Interferon Alpha ELISA Kit following the manufacturer's instructions, and concentration-time data were analyzed by nonlinear-mixed effects modeling as implemented in NONMEM. AUC is given as Time 0 to infinity.

Outcome measures

Measure	End of Therapy QoL assessment completed at end of therapy.	6 Months After End of Therapy QoL assessment completed 6 months after end of therapy.	12 Months After End of Therapy QoL assessment completed 12 months after end of therapy.	Week 2 n=16 Participants QoL assessment completed at Week 2.	Week 4 QoL assessment completed at Week 4.	Week 8 QoL assessment completed at Week 8.	Week 12 QoL assessment completed at Week 12.	Week 24 QoL assessment completed at Week 24.	End of Therapy QoL assessment completed at end of therapy.
Area Under the Curve (AUC) of Interferon ɑ-2b	—	—	—	5026 pcg * hr/ml Interval 2642.0 to 10270.0	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Before first dose, and 1, 2, 4, 6, 8, 12, and 24 hours postinfusion

Population: The pharmacokinetic (PK) analysis of pegylated ɑ-2b included only patients within Stratum A who had PK studies performed. Only one patient had evaluable data in Stratum B and is not included in the final analysis due to differences in clinical variables.

Samples were analyzed for interferon ɑ-2b concentrations by using the VeriKine Human Interferon Alpha ELISA Kit following the manufacturer's instructions, and concentration-time data were analyzed by nonlinear-mixed effects modeling as implemented in NONMEM.

Outcome measures

Measure	End of Therapy QoL assessment completed at end of therapy.	6 Months After End of Therapy QoL assessment completed 6 months after end of therapy.	12 Months After End of Therapy QoL assessment completed 12 months after end of therapy.	Week 2 n=16 Participants QoL assessment completed at Week 2.	Week 4 QoL assessment completed at Week 4.	Week 8 QoL assessment completed at Week 8.	Week 12 QoL assessment completed at Week 12.	Week 24 QoL assessment completed at Week 24.	End of Therapy QoL assessment completed at end of therapy.
Half-Life of Interferon ɑ-2b ɑ half-life	—	—	—	0.7 hours Interval 0.4 to 1.4	—	—	—	—	—
Half-Life of Interferon ɑ-2b ß half-life	—	—	—	14.7 hours Interval 12.5 to 28.2	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Before first dose, and 1, 2, 4, 6, 8, 12, and 24 hours postinfusion

Population: The pharmacokinetic (PK) analysis of pegylated ɑ-2b included only patients within Stratum A who had PK studies performed. Only one patient had evaluable data in Stratum B and is not included in the final analysis due to differences in clinical variables.

Samples were analyzed for interferon ɑ-2b concentrations by using the VeriKine Human Interferon Alpha ELISA Kit following the manufacturer's instructions, and concentration-time data were analyzed by nonlinear-mixed effects modeling as implemented in NONMEM.

Outcome measures

Measure	End of Therapy QoL assessment completed at end of therapy.	6 Months After End of Therapy QoL assessment completed 6 months after end of therapy.	12 Months After End of Therapy QoL assessment completed 12 months after end of therapy.	Week 2 n=16 Participants QoL assessment completed at Week 2.	Week 4 QoL assessment completed at Week 4.	Week 8 QoL assessment completed at Week 8.	Week 12 QoL assessment completed at Week 12.	Week 24 QoL assessment completed at Week 24.	End of Therapy QoL assessment completed at end of therapy.
Volume of Central Compartment (Vc) of Interferon ɑ-2b	—	—	—	25.1 l/m^2 Interval 13.9 to 49.2	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Before first dose, and 1, 2, 4, 6, 8, 12, and 24 hours postinfusion

Population: The pharmacokinetic (PK) analysis of pegylated ɑ-2b included only patients within Stratum A who had PK studies performed. Only one patient had evaluable data in Stratum B and is not included in the final analysis due to differences in clinical variables.

Samples were analyzed for interferon ɑ-2b concentrations by using the VeriKine Human Interferon Alpha ELISA Kit following the manufacturer's instructions, and concentration-time data were analyzed by nonlinear-mixed effects modeling as implemented in NONMEM.

Outcome measures

Measure	End of Therapy QoL assessment completed at end of therapy.	6 Months After End of Therapy QoL assessment completed 6 months after end of therapy.	12 Months After End of Therapy QoL assessment completed 12 months after end of therapy.	Week 2 n=16 Participants QoL assessment completed at Week 2.	Week 4 QoL assessment completed at Week 4.	Week 8 QoL assessment completed at Week 8.	Week 12 QoL assessment completed at Week 12.	Week 24 QoL assessment completed at Week 24.	End of Therapy QoL assessment completed at end of therapy.
Systemic Clearance (CL) of Interferon ɑ-2B	—	—	—	15.3 l/hr/m^2 Interval 7.5 to 29.1	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Pretherapy; Weeks 2, 4, 8, 12, and 24; and End of therapy at 6 months and 12 months post

Population: This QOL analysis included patients only within Stratum A.

QoL assessments were completed using Pediatrics Quality of Life Inventory (PedsQL v4.0). Scale range is 0-100 with higher scores reflecting better quality of life. PedsQL 4.0 healthy sample normative mean ± SD for child report = 83.0 ± 14.8.

Outcome measures

Measure	End of Therapy n=15 Participants QoL assessment completed at end of therapy.	6 Months After End of Therapy n=13 Participants QoL assessment completed 6 months after end of therapy.	12 Months After End of Therapy n=15 Participants QoL assessment completed 12 months after end of therapy.	Week 2 n=15 Participants QoL assessment completed at Week 2.	Week 4 n=15 Participants QoL assessment completed at Week 4.	Week 8 n=17 Participants QoL assessment completed at Week 8.	Week 12 n=14 Participants QoL assessment completed at Week 12.	Week 24 n=14 Participants QoL assessment completed at Week 24.	End of Therapy n=17 Participants QoL assessment completed at end of therapy.
Mean Total PedsQL 4.0 Scores for Child Quality of Life (QoL) Assessments (Stratum A)	80.4 units on a scale Standard Deviation 16.1	87.5 units on a scale Standard Deviation 12.5	91.0 units on a scale Standard Deviation 7.1	75.5 units on a scale Standard Deviation 18.4	71.6 units on a scale Standard Deviation 18.7	77.2 units on a scale Standard Deviation 16.3	79.3 units on a scale Standard Deviation 17.4	77.8 units on a scale Standard Deviation 20.6	80.6 units on a scale Standard Deviation 15.6

OTHER_PRE_SPECIFIED outcome

Timeframe: Pretherapy; Weeks 2, 4, 8, 12, and 24; and End of therapy at 6 months and 12 months post

Population: Only one patient had evaluable data in Stratum B. The raw score, rather than the mean +/- SD, is presented. Data was not collected at Week 24, and the patient was taken off study prior to 6 months after end of therapy.

QoL assessments were completed using Pediatrics Quality of Life Inventory (PedsQL v4.0). Scale range is 0-100 with higher scores reflecting better quality of life. PedsQL 4.0 healthy sample normative mean ± SD for child report = 83.0 ± 14.8.

Outcome measures

Measure	End of Therapy n=1 Participants QoL assessment completed at end of therapy.	6 Months After End of Therapy QoL assessment completed 6 months after end of therapy.	12 Months After End of Therapy QoL assessment completed 12 months after end of therapy.	Week 2 n=1 Participants QoL assessment completed at Week 2.	Week 4 n=1 Participants QoL assessment completed at Week 4.	Week 8 n=1 Participants QoL assessment completed at Week 8.	Week 12 n=1 Participants QoL assessment completed at Week 12.	Week 24 n=1 Participants QoL assessment completed at Week 24.	End of Therapy QoL assessment completed at end of therapy.
Mean Total PedsQL 4.0 Scores for Child Quality of Life (QoL) Assessments (Stratum B)	65.6 units on a scale	—	—	90.3 units on a scale	93.1 units on a scale	72.8 units on a scale	79.2 units on a scale	68.1 units on a scale	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Pretherapy; Weeks 2, 4, 8, 12, and 24; and End of therapy at 6 months and 12 months post

Population: This QOL analysis included patients only within Stratum A.

QoL assessments were completed using Pediatrics Quality of Live Inventory (PedsQL v4.0). Scale range is 0-100 with higher scores reflecting better quality of life. PedsQL 4.0 healthy sample normative mean ± SD for parent report = 87.6 ± 12.3.

Outcome measures

Measure	End of Therapy n=15 Participants QoL assessment completed at end of therapy.	6 Months After End of Therapy n=15 Participants QoL assessment completed 6 months after end of therapy.	12 Months After End of Therapy n=15 Participants QoL assessment completed 12 months after end of therapy.	Week 2 n=16 Participants QoL assessment completed at Week 2.	Week 4 n=15 Participants QoL assessment completed at Week 4.	Week 8 n=17 Participants QoL assessment completed at Week 8.	Week 12 n=13 Participants QoL assessment completed at Week 12.	Week 24 n=16 Participants QoL assessment completed at Week 24.	End of Therapy n=17 Participants QoL assessment completed at end of therapy.
Mean Total PedsQL 4.0 Scores for Parent Quality of Life Assessments (Stratum A)	87.5 units on a scale Standard Deviation 15.3	86.0 units on a scale Standard Deviation 17.6	87.3 units on a scale Standard Deviation 17.5	70.3 units on a scale Standard Deviation 19.1	71.8 units on a scale Standard Deviation 16.4	74.4 units on a scale Standard Deviation 17.9	79.1 units on a scale Standard Deviation 16.6	79.0 units on a scale Standard Deviation 19.0	82.2 units on a scale Standard Deviation 14.5

OTHER_PRE_SPECIFIED outcome

Timeframe: Pretherapy; Weeks 2, 4, 8, 12, and 24; and End of therapy at 6 months and 12 months post

Population: Only one patient had evaluable data in Stratum B. The raw score, rather than the mean +/- SD, is presented. Data was not collected after Week 4.

QoL assessments were completed using Pediatrics Quality of Live Inventory (PedsQL v4.0). Scale range is 0-100 with higher scores reflecting better quality of life. PedsQL 4.0 healthy sample normative mean ± SD for parent report = 87.6 ± 12.3.

Outcome measures

Measure	End of Therapy QoL assessment completed at end of therapy.	6 Months After End of Therapy QoL assessment completed 6 months after end of therapy.	12 Months After End of Therapy QoL assessment completed 12 months after end of therapy.	Week 2 n=1 Participants QoL assessment completed at Week 2.	Week 4 n=1 Participants QoL assessment completed at Week 4.	Week 8 n=1 Participants QoL assessment completed at Week 8.	Week 12 QoL assessment completed at Week 12.	Week 24 QoL assessment completed at Week 24.	End of Therapy QoL assessment completed at end of therapy.
Mean Total PedsQL 4.0 Scores for Parent Quality of Life Assessments (Stratum B)	—	—	—	77.6 units on a scale	72.2 units on a scale	89.1 units on a scale	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Weeks 2, 4, 8, 12, and 24; and End of therapy at 6 months and 12 months post

Population: PedsQL v3.0 was not completed pretherapy. This QOL analysis included patients only within Stratum A.

QoL assessments were completed using Pediatrics Cancer Quality of Life Inventory (PedsQL v3.0). Scale range is 0-100 with higher scores reflecting better quality of life.

Outcome measures

Measure	End of Therapy n=15 Participants QoL assessment completed at end of therapy.	6 Months After End of Therapy n=15 Participants QoL assessment completed 6 months after end of therapy.	12 Months After End of Therapy QoL assessment completed 12 months after end of therapy.	Week 2 n=17 Participants QoL assessment completed at Week 2.	Week 4 n=19 Participants QoL assessment completed at Week 4.	Week 8 n=17 Participants QoL assessment completed at Week 8.	Week 12 n=17 Participants QoL assessment completed at Week 12.	Week 24 n=16 Participants QoL assessment completed at Week 24.	End of Therapy n=17 Participants QoL assessment completed at end of therapy.
Mean Total PedsQL 3.0 Scores for Child Cancer Quality of Life (QoL) Assessments (Stratum A)	83.7 units on a scale Standard Deviation 18.0	85.4 units on a scale Standard Deviation 8.9	—	71.1 units on a scale Standard Deviation 17.2	76.1 units on a scale Standard Deviation 15.4	79.2 units on a scale Standard Deviation 19.2	78.5 units on a scale Standard Deviation 14.7	77.1 units on a scale Standard Deviation 16.0	77.0 units on a scale Standard Deviation 16.5

OTHER_PRE_SPECIFIED outcome

Timeframe: Weeks 2, 4, 8, 12, and 24; and End of therapy at 6 months and 12 months post

Population: PedsQL v3.0 was not completed pretherapy. Only one patient had evaluable data in Stratum B. The raw score, rather than the mean +/- SD, is presented. Data was not collected at Week 24, and the patient was taken off study prior to 6 months after end of therapy.

QoL assessments were completed using Pediatrics Cancer Quality of Life Inventory (PedsQL v3.0). Scale range is 0-100 with higher scores reflecting better quality of life.

Outcome measures

Measure	End of Therapy QoL assessment completed at end of therapy.	6 Months After End of Therapy QoL assessment completed 6 months after end of therapy.	12 Months After End of Therapy QoL assessment completed 12 months after end of therapy.	Week 2 n=1 Participants QoL assessment completed at Week 2.	Week 4 n=1 Participants QoL assessment completed at Week 4.	Week 8 n=1 Participants QoL assessment completed at Week 8.	Week 12 n=1 Participants QoL assessment completed at Week 12.	Week 24 QoL assessment completed at Week 24.	End of Therapy n=1 Participants QoL assessment completed at end of therapy.
Mean Total PedsQL 3.0 Scores for Child Cancer Quality of Life (QoL) Assessments (Stratum B)	—	—	—	92.8 units on a scale	90.1 units on a scale	93.2 units on a scale	79.6 units on a scale	—	67.4 units on a scale

OTHER_PRE_SPECIFIED outcome

Timeframe: Weeks 2, 4, 8, 12, and 24; and End of therapy at 6 months and 12 months post

Population: PedsQL v3.0 was not completed pretherapy. This QOL analysis included patients only within Stratum A.

QoL assessments were completed using Pediatrics Cancer Quality of Life Inventory (PedsQL v3.0). Scale range is 0-100 with higher scores reflecting better quality of life.

Outcome measures

Measure	End of Therapy n=15 Participants QoL assessment completed at end of therapy.	6 Months After End of Therapy n=15 Participants QoL assessment completed 6 months after end of therapy.	12 Months After End of Therapy QoL assessment completed 12 months after end of therapy.	Week 2 n=19 Participants QoL assessment completed at Week 2.	Week 4 n=19 Participants QoL assessment completed at Week 4.	Week 8 n=17 Participants QoL assessment completed at Week 8.	Week 12 n=18 Participants QoL assessment completed at Week 12.	Week 24 n=16 Participants QoL assessment completed at Week 24.	End of Therapy n=16 Participants QoL assessment completed at end of therapy.
Mean Total PedsQL 3.0 Scores for Parent Cancer Quality of Life (QoL) Assessments (Stratum A)	85.0 units on a scale Standard Deviation 11.5	89.1 units on a scale Standard Deviation 11.6	—	73.2 units on a scale Standard Deviation 13.9	75.1 units on a scale Standard Deviation 15.2	81.4 units on a scale Standard Deviation 11.6	78.7 units on a scale Standard Deviation 17.7	81.6 units on a scale Standard Deviation 17.1	85.6 units on a scale Standard Deviation 13.8

OTHER_PRE_SPECIFIED outcome

Timeframe: Weeks 2, 4, 8, 12, and 24; and End of therapy at 6 months and 12 months post

Population: PedsQL v3.0 was not completed pretherapy. Only one patient had evaluable data in Stratum B. The raw score, rather than the mean +/- SD, is presented. Data was not collected after Week 4.

QoL assessments were completed using Pediatrics Cancer Quality of Life Inventory (PedsQL v3.0). Scale range is 0-100 with higher scores reflecting better quality of life.

Outcome measures

Measure	End of Therapy QoL assessment completed at end of therapy.	6 Months After End of Therapy QoL assessment completed 6 months after end of therapy.	12 Months After End of Therapy QoL assessment completed 12 months after end of therapy.	Week 2 n=1 Participants QoL assessment completed at Week 2.	Week 4 n=1 Participants QoL assessment completed at Week 4.	Week 8 QoL assessment completed at Week 8.	Week 12 QoL assessment completed at Week 12.	Week 24 QoL assessment completed at Week 24.	End of Therapy QoL assessment completed at end of therapy.
Mean Total PedsQL 3.0 Scores for Parent Cancer Quality of Life (QoL) Assessments (Stratum B)	—	—	—	67.7 units on a scale	71.4 units on a scale	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Pretherapy, Week 4, Week 24, End of Therapy, and 6 Months Post End of Therapy

Population: This QOL analysis included patients only within Stratum A.

The Behavioral Assessment System for Children, 2nd Edition (BASC-2) was administered to parents, assessing for any effects on behavior or mood in children undergoing study therapy. The behavior system index (BSI) T-score (range 0-100) is reported for the BASC-2 assessment. Higher scores reflect greater behavioral problems.

Outcome measures

Measure	End of Therapy QoL assessment completed at end of therapy.	6 Months After End of Therapy QoL assessment completed 6 months after end of therapy.	12 Months After End of Therapy QoL assessment completed 12 months after end of therapy.	Week 2 n=21 Participants QoL assessment completed at Week 2.	Week 4 n=21 Participants QoL assessment completed at Week 4.	Week 8 n=19 Participants QoL assessment completed at Week 8.	Week 12 n=18 Participants QoL assessment completed at Week 12.	Week 24 n=16 Participants QoL assessment completed at Week 24.	End of Therapy QoL assessment completed at end of therapy.
BASC-2 Psychological Assessment (Stratum A)	—	—	—	44.9 T score Standard Deviation 8.1	45.9 T score Standard Deviation 8.3	44.2 T score Standard Deviation 6.9	47.2 T score Standard Deviation 11.1	42.3 T score Standard Deviation 7.2	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Pretherapy, Week 4, Week 24, End of Therapy, and 6 Months Post End of Therapy

Population: Only one patient had evaluable data in Stratum B, but scores were not available for this instrument due to the age of the patient.

The Behavioral Assessment System for Children, 2nd Edition (BASC-2) was administered to parents, assessing for any effects on behavior or mood in children undergoing study therapy. The behavior system index (BSI) T-score (range 0-100) is reported for the BASC-2 assessment. Higher scores reflect greater behavioral problems.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Pretherapy, Week 4, Week 24, End of Therapy, and 6 Months Post End of Therapy

Population: This QOL analysis included patients only within Stratum A.

The Behavioral Rating Inventory of Executive Function (BRIEF) was administered to parents, assessing for any effects on behavior or mood in children undergoing study therapy. The global executive composite (GEC) T-score (range 0-100) is reported for the BRIEF assessment. Higher scores reflect poorer executive function.

Outcome measures

Measure	End of Therapy QoL assessment completed at end of therapy.	6 Months After End of Therapy QoL assessment completed 6 months after end of therapy.	12 Months After End of Therapy QoL assessment completed 12 months after end of therapy.	Week 2 n=17 Participants QoL assessment completed at Week 2.	Week 4 n=17 Participants QoL assessment completed at Week 4.	Week 8 n=13 Participants QoL assessment completed at Week 8.	Week 12 n=14 Participants QoL assessment completed at Week 12.	Week 24 n=11 Participants QoL assessment completed at Week 24.	End of Therapy QoL assessment completed at end of therapy.
BRIEF Psychological Assessment (Stratum A)	—	—	—	47.9 T score Standard Deviation 12.8	50.8 T score Standard Deviation 11.9	48.6 T score Standard Deviation 12.4	47.6 T score Standard Deviation 12.6	42.6 T score Standard Deviation 8.1	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Pretherapy, Week 4, Week 24, End of Therapy, and 6 Months Post End of Therapy

Population: Only one patient had evaluable data in Stratum B, but scores were not available for this instrument due to the age of the patient.

The Behavioral Rating Inventory of Executive Function (BRIEF) was administered to parents, assessing for any effects on behavior or mood in children undergoing study therapy. The global executive composite (GEC) T-score (range 0-100) is reported for the BRIEF assessment. Higher scores reflect poorer executive function.

Outcome measures

Outcome data not reported

Adverse Events

Peginterferon ɑ-2b/Non-pegylated Interferon ɑ-2b

Serious events: 3 serious events

Other events: 23 other events

Deaths: 0 deaths

Temozolomide/Peginterferon ɑ-2b With Measureable Disease

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Temozolomide/Peginterferon ɑ-2b Without Measureable Disease

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Measure	Peginterferon ɑ-2b/Non-pegylated Interferon ɑ-2b n=23 participants at risk Stratum A: American Joint Committee on Cancer (AJCC) resected Stages IIC, IIIA, and IIIB Participants received recombinant interferon ɑ-2b 20 million units/m\^2/day intravenously 5 consecutive days per week for 4 weeks followed by peginterferon ɑ-2b 1 mcg/kg subcutaneously once a week for 48 weeks.	Temozolomide/Peginterferon ɑ-2b With Measureable Disease n=2 participants at risk Stratum B1: American Joint Committee on Cancer (AJCC) resected Stage IIIC, unresectable Stage III, Stage IV, and recurrent participants with measurable disease Participants received 8 weekly doses of peginterferon ɑ-2b 0.5 mcg/kg/dose subcutaneously in combination with temozolomide 75 mg/m\^2/dose by mouth daily for 6 weeks followed by 2 week break. The duration of each treatment course was 8 weeks.	Temozolomide/Peginterferon ɑ-2b Without Measureable Disease n=4 participants at risk Stratum B2: American Joint Committee on Cancer (AJCC) resected Stage IIIC, unresectable Stage III, Stage IV, and recurrent participants without measurable disease Participants received 8 weekly doses of peginterferon ɑ-2b 0.5 mcg/kg/dose subcutaneously in combination with temozolomide 75 mg/m\^2/dose by mouth daily for 6 weeks followed by 2 week break. The duration of each treatment course was 8 weeks. Stratum B2 (no measurable disease) proceeded with 7 courses as outlined.
Musculoskeletal and connective tissue disorders Joint effusion	4.3% 1/23 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Nervous system disorders Confusion	4.3% 1/23 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Musculoskeletal and connective tissue disorders Joint function	4.3% 1/23 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Nervous system disorders Extrapyramidal/involuntary movement/restlessness	4.3% 1/23 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Nervous system disorders Mood alteration, agitation	4.3% 1/23 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Nervous system disorders Psychosis (hallucinations/delusions)	4.3% 1/23 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Nervous system disorders Seizure	4.3% 1/23 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.

Other adverse events

Measure	Peginterferon ɑ-2b/Non-pegylated Interferon ɑ-2b n=23 participants at risk Stratum A: American Joint Committee on Cancer (AJCC) resected Stages IIC, IIIA, and IIIB Participants received recombinant interferon ɑ-2b 20 million units/m\^2/day intravenously 5 consecutive days per week for 4 weeks followed by peginterferon ɑ-2b 1 mcg/kg subcutaneously once a week for 48 weeks.	Temozolomide/Peginterferon ɑ-2b With Measureable Disease n=2 participants at risk Stratum B1: American Joint Committee on Cancer (AJCC) resected Stage IIIC, unresectable Stage III, Stage IV, and recurrent participants with measurable disease Participants received 8 weekly doses of peginterferon ɑ-2b 0.5 mcg/kg/dose subcutaneously in combination with temozolomide 75 mg/m\^2/dose by mouth daily for 6 weeks followed by 2 week break. The duration of each treatment course was 8 weeks.	Temozolomide/Peginterferon ɑ-2b Without Measureable Disease n=4 participants at risk Stratum B2: American Joint Committee on Cancer (AJCC) resected Stage IIIC, unresectable Stage III, Stage IV, and recurrent participants without measurable disease Participants received 8 weekly doses of peginterferon ɑ-2b 0.5 mcg/kg/dose subcutaneously in combination with temozolomide 75 mg/m\^2/dose by mouth daily for 6 weeks followed by 2 week break. The duration of each treatment course was 8 weeks. Stratum B2 (no measurable disease) proceeded with 7 courses as outlined.
Gastrointestinal disorders Diarrhea	56.5% 13/23 • Number of events 32 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	50.0% 1/2 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	100.0% 4/4 • Number of events 9 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Gastrointestinal disorders Flatulence	4.3% 1/23 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	50.0% 1/2 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Cardiac disorders Supraventricular and nodal arrhythmia, sinus tachycardia	39.1% 9/23 • Number of events 22 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	100.0% 2/2 • Number of events 4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	25.0% 1/4 • Number of events 3 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Cardiac disorders Hypertension	26.1% 6/23 • Number of events 21 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	50.0% 2/4 • Number of events 2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
General disorders Fatigue (asthenia, lethargy, malaise)	87.0% 20/23 • Number of events 100 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	75.0% 3/4 • Number of events 4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Gastrointestinal disorders Heartburn/dyspepsia	8.7% 2/23 • Number of events 3 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	25.0% 1/4 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Skin and subcutaneous tissue disorders Hair loss/alopecia (scalp or body)	30.4% 7/23 • Number of events 8 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	25.0% 1/4 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
General disorders Fever (in the absence of neutropenia, where neutropenia is defined as ANC<1.0 x 10e9/L)	69.6% 16/23 • Number of events 39 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	50.0% 1/2 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	50.0% 2/4 • Number of events 3 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Blood and lymphatic system disorders Platelets	65.2% 15/23 • Number of events 28 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	75.0% 3/4 • Number of events 18 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Cardiac disorders Supraventricular and nodal arrhythmia, sinus bradycardia	34.8% 8/23 • Number of events 20 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	25.0% 1/4 • Number of events 3 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Immune system disorders Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	47.8% 11/23 • Number of events 19 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	50.0% 2/4 • Number of events 2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Blood and lymphatic system disorders Hemoglobin	56.5% 13/23 • Number of events 29 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	100.0% 2/2 • Number of events 2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	50.0% 2/4 • Number of events 11 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Blood and lymphatic system disorders Leukocytes) total WBC)	95.7% 22/23 • Number of events 116 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	100.0% 2/2 • Number of events 4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	100.0% 4/4 • Number of events 16 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Blood and lymphatic system disorders Neutrophils/granulocytes (ANC/AGC)	100.0% 23/23 • Number of events 142 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	100.0% 4/4 • Number of events 16 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
General disorders Rigors/chills	43.5% 10/23 • Number of events 19 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
General disorders Sweating (diaphoresis)	8.7% 2/23 • Number of events 5 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
General disorders Weight gain	8.7% 2/23 • Number of events 2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
General disorders Weight loss	17.4% 4/23 • Number of events 9 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	50.0% 1/2 • Number of events 2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	25.0% 1/4 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Skin and subcutaneous tissue disorders Bruising (in absence of Grade 3 or 4 thrombocytopenia)	17.4% 4/23 • Number of events 9 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Skin and subcutaneous tissue disorders Dermatology/skin - other	17.4% 4/23 • Number of events 7 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Skin and subcutaneous tissue disorders Dry skin	26.1% 6/23 • Number of events 6 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Skin and subcutaneous tissue disorders Flushing	13.0% 3/23 • Number of events 7 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	25.0% 1/4 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Skin and subcutaneous tissue disorders Photosensitivity	4.3% 1/23 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	25.0% 1/4 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Skin and subcutaneous tissue disorders Pruritus/itching	21.7% 5/23 • Number of events 5 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	50.0% 1/2 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	25.0% 1/4 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Skin and subcutaneous tissue disorders Rash/desquamation	87.0% 20/23 • Number of events 83 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	50.0% 1/2 • Number of events 2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	75.0% 3/4 • Number of events 5 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Skin and subcutaneous tissue disorders Urticaria (hives, welts, wheals)	0.00% 0/23 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	50.0% 1/2 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Endocrine disorders Hot flashes/flushes	13.0% 3/23 • Number of events 3 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Endocrine disorders Thyroid function, low (hypothyroidism)	13.0% 3/23 • Number of events 5 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Gastrointestinal disorders Anorexia	78.3% 18/23 • Number of events 42 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	100.0% 2/2 • Number of events 2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	50.0% 2/4 • Number of events 3 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Gastrointestinal disorders Constipation	39.1% 9/23 • Number of events 18 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Gastrointestinal disorders Dehydration	8.7% 2/23 • Number of events 2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Gastrointestinal disorders Mucositis/stomatitis (clinical exam), oral cavity	13.0% 3/23 • Number of events 3 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Gastrointestinal disorders Nausea	73.9% 17/23 • Number of events 38 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	100.0% 4/4 • Number of events 9 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Gastrointestinal disorders Taste alteration (dysgeusia)	8.7% 2/23 • Number of events 3 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Gastrointestinal disorders Vomiting	52.2% 12/23 • Number of events 30 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	75.0% 3/4 • Number of events 17 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Vascular disorders Hemorrhage, GI, lower GI NOS	13.0% 3/23 • Number of events 4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Vascular disorders Hemorrhage, GI, oral cavity	8.7% 2/23 • Number of events 2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Vascular disorders Hemorrhage, GI, rectum	8.7% 2/23 • Number of events 2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Vascular disorders Hemorrhage, GI, upper GI NOS	0.00% 0/23 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	25.0% 1/4 • Number of events 2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Vascular disorders Hemorrhage, pulmonary/upper respiratory, nose	13.0% 3/23 • Number of events 7 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Vascular disorders Hemorrhage/bleeding - other	8.7% 2/23 • Number of events 3 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils, lip/perioral	0.00% 0/23 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	25.0% 1/4 • Number of events 2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils, middle ear (otitis media)	8.7% 2/23 • Number of events 2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils, nerve-peripheral	0.00% 0/23 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	25.0% 1/4 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils, sinus	8.7% 2/23 • Number of events 2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils, upper airway NOS	13.0% 3/23 • Number of events 4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	25.0% 1/4 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Infections and infestations Infection with unknown ANC, sinus	8.7% 2/23 • Number of events 2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Blood and lymphatic system disorders Edema: head and neck	0.00% 0/23 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	25.0% 1/4 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Blood and lymphatic system disorders Edema: limb	8.7% 2/23 • Number of events 5 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	25.0% 1/4 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Blood and lymphatic system disorders Edema: trunk/genital	13.0% 3/23 • Number of events 3 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Blood and lymphatic system disorders Lymphatics - other	4.3% 1/23 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	25.0% 1/4 • Number of events 2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Metabolism and nutrition disorders ALT, SGPT (serum gluatmic pyruvic transaminase)	95.7% 22/23 • Number of events 90 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	50.0% 2/4 • Number of events 10 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Metabolism and nutrition disorders AST, SGOT (serum glutamic oxaloacetic transaminase)	100.0% 23/23 • Number of events 73 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	50.0% 1/2 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	25.0% 1/4 • Number of events 3 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Metabolism and nutrition disorders Albumin, serum-low (hypoalbuminemia)	26.1% 6/23 • Number of events 6 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	50.0% 1/2 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	25.0% 1/4 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Metabolism and nutrition disorders Alkaline phosphatase	17.4% 4/23 • Number of events 6 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Metabolism and nutrition disorders Amylase	34.8% 8/23 • Number of events 14 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	25.0% 1/4 • Number of events 4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Metabolism and nutrition disorders Calcium, serum-high (hypercalcemia)	0.00% 0/23 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	50.0% 1/2 • Number of events 2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Metabolism and nutrition disorders Calcium, serum-low (hypocalcemia	13.0% 3/23 • Number of events 5 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Metabolism and nutrition disorders Glucose, serum-high (hyperglycemia)	52.2% 12/23 • Number of events 23 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	50.0% 1/2 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	50.0% 2/4 • Number of events 5 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Metabolism and nutrition disorders Glucose, serum-low (hypoglycemia)	43.5% 10/23 • Number of events 14 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	25.0% 1/4 • Number of events 3 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Metabolism and nutrition disorders Lipase	13.0% 3/23 • Number of events 4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	50.0% 2/4 • Number of events 5 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Metabolism and nutrition disorders Magnesium, serum-high (hypermagnesemia)	26.1% 6/23 • Number of events 9 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Metabolism and nutrition disorders Magnesium, serum-low (hypomagnesemia)	13.0% 3/23 • Number of events 8 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Metabolism and nutrition disorders Metabolic/laboratory - other	30.4% 7/23 • Number of events 23 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Metabolism and nutrition disorders Potassium, serum-high (hyperkalemia	21.7% 5/23 • Number of events 9 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	50.0% 2/4 • Number of events 8 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Metabolism and nutrition disorders Potassium, serum-low (hypokalemia)	17.4% 4/23 • Number of events 4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	50.0% 2/4 • Number of events 2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Metabolism and nutrition disorders Proteinuria	4.3% 1/23 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	25.0% 1/4 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Metabolism and nutrition disorders Sodium, serum-high (hypernatremia)	39.1% 9/23 • Number of events 17 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	50.0% 2/4 • Number of events 2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Metabolism and nutrition disorders Triglyceride, serum-high (hypertriglyceridemia)	47.8% 11/23 • Number of events 17 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	25.0% 1/4 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Metabolism and nutrition disorders Uric acid, serum-high (hyperuricemia)	30.4% 7/23 • Number of events 7 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	75.0% 3/4 • Number of events 9 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Nervous system disorders Dizziness	13.0% 3/23 • Number of events 5 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Nervous system disorders Mood alteration, agitation	39.1% 9/23 • Number of events 23 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Nervous system disorders Mood alteration, anxiety	13.0% 3/23 • Number of events 3 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	25.0% 1/4 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Nervous system disorders Mood alteration, depression	13.0% 3/23 • Number of events 4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Nervous system disorders Neuropathy: sensory	21.7% 5/23 • Number of events 8 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Nervous system disorders Personality/behavioral	8.7% 2/23 • Number of events 2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Eye disorders Ocular surface disease	8.7% 2/23 • Number of events 3 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Eye disorders Ocular/visual - other	8.7% 2/23 • Number of events 3 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Eye disorders Vision-blurred vision	4.3% 1/23 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	25.0% 1/4 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Respiratory, thoracic and mediastinal disorders Bronchospasm, wheezing	0.00% 0/23 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	25.0% 1/4 • Number of events 6 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Respiratory, thoracic and mediastinal disorders Cough	26.1% 6/23 • Number of events 8 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	25.0% 1/4 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	0.00% 0/23 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	25.0% 1/4 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Renal and urinary disorders Incontinence, urinary	4.3% 1/23 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	25.0% 1/4 • Number of events 2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Renal and urinary disorders Urinary frequency/urgency	4.3% 1/23 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	25.0% 1/4 • Number of events 2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Reproductive system and breast disorders Irregular menses (change from baseline)	8.7% 2/23 • Number of events 3 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
General disorders Pain, abdomen NOS	34.8% 8/23 • Number of events 16 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	50.0% 1/2 • Number of events 2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	50.0% 2/4 • Number of events 5 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
General disorders Pain, back	13.0% 3/23 • Number of events 22 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	50.0% 1/2 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	50.0% 2/4 • Number of events 2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
General disorders Pain, chest wall	8.7% 2/23 • Number of events 2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	25.0% 1/4 • Number of events 4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
General disorders Pain, chest/thorax NOS	13.0% 3/23 • Number of events 5 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	50.0% 2/4 • Number of events 3 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
General disorders Pain, dental/teeth/peridontal	8.7% 2/23 • Number of events 2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
General disorders Pain, external ear	8.7% 2/23 • Number of events 2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
General disorders Pain, extremity-limb	52.2% 12/23 • Number of events 27 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	50.0% 1/2 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
General disorders Pain, head/headache	78.3% 18/23 • Number of events 257 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	50.0% 1/2 • Number of events 2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	50.0% 2/4 • Number of events 6 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
General disorders Pain, joint	13.0% 3/23 • Number of events 4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
General disorders Pain, muscle	26.1% 6/23 • Number of events 12 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	25.0% 1/4 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
General disorders Pain, neck	13.0% 3/23 • Number of events 3 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
General disorders Pain, pain NOS	34.8% 8/23 • Number of events 43 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
General disorders Pain, stomach	13.0% 3/23 • Number of events 3 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
General disorders Pain, throat/pharynx/larynx	30.4% 7/23 • Number of events 9 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils, Lung (pnemonia)	0.00% 0/23 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	25.0% 1/4 • Number of events 1 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.
Metabolism and nutrition disorders Bilirubin (hyperbilirubinemia)	8.7% 2/23 • Number of events 6 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/2 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.	0.00% 0/4 • Adverse events are reported from the start of treatment for the first patient in May 2008 through April 2016.

Additional Information

Alberto Pappo, MD

St. Jude Children's Research Hospital

Phone: 901-595-2322

Email: info@stjude.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place