Trial Outcomes & Findings for A Phase II Study of Selinexor Plus Cytarabine and Idarubicin in Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML) (NCT NCT02249091)

NCT ID: NCT02249091

Last Updated: 2021-08-25

Results Overview

Efficacy of selinexor in combination with standard chemotherapy in patients with relapsed/refractory AML by determination of rate of complete response (CR) or morphologic complete response with incomplete blood count recovery (CRi), as defined by the recommendations on diagnosis and management of AML in adults from an international expert panel, on behalf of the European LeukemiaNet: CR: Absolute Neutrophil count (ANC) \>1.0x10\^9/L, Platelet count \>100x10\^9/L, Bone marrow blasts \<5%, no Auer rods, no evidence of extramedullary disease. CRi: Same as CR, but ANC may be \<1.0x10\^9/L and/or Platelet count \<100x10\^9/L. Patients with morphologic leukemia free-state (MLFS) were included in the group of responders. MLFS: Bone marrow blasts \<5%, no Auer rods, no evidence of extramedullary disease. The best response after Selinexor treatment was analyzed, thus the best response after the induction cycle(s).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 42 participants
• Primary outcome timeframe: 1-2 induction cycles (4 - 8 weeks)
• Results posted on: 2021-08-25

Participant Flow

43 patients were registered in the clinical trial at 3 sites. One patient was a screening failure. Of the remaining 42 patients, the first 27 patients were treated in cohort 1 (Selinexor dosed by Body Surface Area [BSA] 40 mg/m^2 per dose) and the other 15 patients were treated in cohort 2 (flat dose of Selinexor of 60 mg per dose).

Participant milestones

Measure	Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows: Selinexor: 40 mg/m\^2 twice weekly orally starting on day 2 (total of 8 doses per 4-week induction cycle). Idarubcin: i.v. infusion, 10 mg/m\^2, on days 1,3,5 in cycle 1 Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m\^2 Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.	Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows: Selinexor: 60 mg flat dose twice weekly orally during weeks 1-3 of a 4-week cycle (day 2, 4, 9, 11, 16, 18; total of 6 doses per 4-week induction cycle). Idarubcin: i.v. infusion, 10 mg/m\^2, on days 1,3,5 in cycle 1. Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m\^2 Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.
Overall Study STARTED	27	15
Overall Study COMPLETED	7	2
Overall Study NOT COMPLETED	20	13

Reasons for withdrawal

Measure	Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows: Selinexor: 40 mg/m\^2 twice weekly orally starting on day 2 (total of 8 doses per 4-week induction cycle). Idarubcin: i.v. infusion, 10 mg/m\^2, on days 1,3,5 in cycle 1 Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m\^2 Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.	Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows: Selinexor: 60 mg flat dose twice weekly orally during weeks 1-3 of a 4-week cycle (day 2, 4, 9, 11, 16, 18; total of 6 doses per 4-week induction cycle). Idarubcin: i.v. infusion, 10 mg/m\^2, on days 1,3,5 in cycle 1. Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m\^2 Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.
Overall Study Lack of Efficacy	8	3
Overall Study Physician Decision	4	1
Overall Study Withdrawal by Subject	2	2
Overall Study Death	3	4
Overall Study Adverse Event	1	0
Overall Study Stable disease with following SCT	0	1
Overall Study Ongoing bone marrow aplasia, periph. pancytopenia	0	1
Overall Study CR with subsequent donor lymphocyte infusion	1	0
Overall Study Refractory AML	1	1

Baseline Characteristics

A Phase II Study of Selinexor Plus Cytarabine and Idarubicin in Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML)

Baseline characteristics by cohort

Measure	Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin n=27 Participants Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows: Selinexor: 40 mg/m\^2 twice weekly orally starting on day 2 (total of 8 doses per 4-week induction cycle). Idarubcin: i.v. infusion, 10 mg/m\^2, on days 1,3,5 in cycle 1 Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m\^2 Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.	Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin n=15 Participants Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows: Selinexor: 60 mg flat dose twice weekly orally during weeks 1-3 of a 4-week cycle (day 2, 4, 9, 11, 16, 18; total of 6 doses per 4-week induction cycle). Idarubcin: i.v. infusion, 10 mg/m\^2, on days 1,3,5 in cycle 1. Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m\^2 Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.	Total n=42 Participants Total of all reporting groups
Age, Continuous	54.0 years STANDARD_DEVIATION 15.18 • n=5 Participants	58.5 years STANDARD_DEVIATION 13.55 • n=7 Participants	55.6 years STANDARD_DEVIATION 14.62 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	6 Participants n=7 Participants	17 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	9 Participants n=7 Participants	25 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	27 Participants n=5 Participants	14 Participants n=7 Participants	41 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Germany	27 participants n=5 Participants	15 participants n=7 Participants	42 participants n=5 Participants
Leukemia diagnosis De Novo Acute Myeloid Leukemia (AML)	19 Participants n=5 Participants	12 Participants n=7 Participants	31 Participants n=5 Participants
Leukemia diagnosis Therapy-induced AML	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Leukemia diagnosis Secondary AML	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Prior stem cell transplantation (SCT)	10 Participants n=5 Participants	7 Participants n=7 Participants	17 Participants n=5 Participants

PRIMARY outcome

Timeframe: 1-2 induction cycles (4 - 8 weeks)

Population: All patients who have received study medication at least once and for whom post-baseline efficacy data upon treatment was available.

Efficacy of selinexor in combination with standard chemotherapy in patients with relapsed/refractory AML by determination of rate of complete response (CR) or morphologic complete response with incomplete blood count recovery (CRi), as defined by the recommendations on diagnosis and management of AML in adults from an international expert panel, on behalf of the European LeukemiaNet:

CR: Absolute Neutrophil count (ANC) >1.0x10^9/L, Platelet count >100x10^9/L, Bone marrow blasts <5%, no Auer rods, no evidence of extramedullary disease.

CRi: Same as CR, but ANC may be <1.0x10^9/L and/or Platelet count <100x10^9/L.

Patients with morphologic leukemia free-state (MLFS) were included in the group of responders. MLFS: Bone marrow blasts <5%, no Auer rods, no evidence of extramedullary disease.

The best response after Selinexor treatment was analyzed, thus the best response after the induction cycle(s).

Outcome measures

Measure	Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin n=27 Participants Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows: Selinexor: 40 mg/m\^2 twice weekly orally starting on day 2 (total of 8 doses per 4-week induction cycle). Idarubcin: i.v. infusion, 10 mg/m\^2, on days 1,3,5 in cycle 1 Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m\^2 Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.	Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin n=15 Participants Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows: Selinexor: 60 mg flat dose twice weekly orally during weeks 1-3 of a 4-week cycle (day 2, 4, 9, 11, 16, 18; total of 6 doses per 4-week induction cycle). Idarubcin: i.v. infusion, 10 mg/m\^2, on days 1,3,5 in cycle 1. Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m\^2 Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.
Number of Participants With CR/CRi = Overall Reponse Rate	15 Participants	6 Participants

SECONDARY outcome

Timeframe: 1-2 induction cycles (4 - 8 weeks)

Population: All patients who have received study medication at least once and for whom post-baseline efficacy data upon treatment was available.

Efficacy of selinexor in combination with standard chemotherapy in patients with relapsed/refractory AML by determination of rate of partial remission(PR) as defined by the recommendations on diagnosis and management of AML in adults from an international expert panel, on behalf of the European LeukemiaNet:

PR: Absolute Neutrophil count (ANC) >1.0x10^9/L, Platelet count >100x10^9/L, at least a 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts <5% with persistent Auer rods.

The best response after Selinexor treatment was analyzed, thus the best response after the induction cycle(s).

Outcome measures

Measure	Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin n=27 Participants Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows: Selinexor: 40 mg/m\^2 twice weekly orally starting on day 2 (total of 8 doses per 4-week induction cycle). Idarubcin: i.v. infusion, 10 mg/m\^2, on days 1,3,5 in cycle 1 Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m\^2 Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.	Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin n=15 Participants Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows: Selinexor: 60 mg flat dose twice weekly orally during weeks 1-3 of a 4-week cycle (day 2, 4, 9, 11, 16, 18; total of 6 doses per 4-week induction cycle). Idarubcin: i.v. infusion, 10 mg/m\^2, on days 1,3,5 in cycle 1. Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m\^2 Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.
Number of Participants With Partial Remission (PR) = Rate of PR	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 1-2 induction cycles (4 - 8 weeks)

Population: All patients who have received study medication at least once and for whom post-baseline efficacy data upon treatment was available.

Percentage of patients being transplanted after induction therapy (stem cell transplantation)

Outcome measures

Measure	Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin n=27 Participants Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows: Selinexor: 40 mg/m\^2 twice weekly orally starting on day 2 (total of 8 doses per 4-week induction cycle). Idarubcin: i.v. infusion, 10 mg/m\^2, on days 1,3,5 in cycle 1 Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m\^2 Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.	Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin n=15 Participants Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows: Selinexor: 60 mg flat dose twice weekly orally during weeks 1-3 of a 4-week cycle (day 2, 4, 9, 11, 16, 18; total of 6 doses per 4-week induction cycle). Idarubcin: i.v. infusion, 10 mg/m\^2, on days 1,3,5 in cycle 1. Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m\^2 Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.
Percentage of Patients Transplanted After Induction Therapy (Stem Cell Transplantation)	11 Participants	4 Participants

SECONDARY outcome

Timeframe: 1 induction cycle (4 weeks)

Population: All patients who have received study medication at least once and for whom post-baseline efficacy data upon treatment was available.

Early death was defined as death before the end of the first induction cycle.

Outcome measures

Measure	Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin n=27 Participants Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows: Selinexor: 40 mg/m\^2 twice weekly orally starting on day 2 (total of 8 doses per 4-week induction cycle). Idarubcin: i.v. infusion, 10 mg/m\^2, on days 1,3,5 in cycle 1 Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m\^2 Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.	Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin n=15 Participants Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows: Selinexor: 60 mg flat dose twice weekly orally during weeks 1-3 of a 4-week cycle (day 2, 4, 9, 11, 16, 18; total of 6 doses per 4-week induction cycle). Idarubcin: i.v. infusion, 10 mg/m\^2, on days 1,3,5 in cycle 1. Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m\^2 Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.
Early Death Rate	0 Participants	4 Participants

SECONDARY outcome

Timeframe: Time from registration to event, max 2 years

Population: All patients who have received study medication at least once and for whom post-baseline efficacy data upon treatment was available.

Overall survival (OS) was calculated from the date of informed consent to the date of death. Patients still alive at the end of follow-up were censored at the last date of follow-up.

Outcome measures

Measure	Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin n=27 Participants Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows: Selinexor: 40 mg/m\^2 twice weekly orally starting on day 2 (total of 8 doses per 4-week induction cycle). Idarubcin: i.v. infusion, 10 mg/m\^2, on days 1,3,5 in cycle 1 Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m\^2 Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.	Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin n=15 Participants Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows: Selinexor: 60 mg flat dose twice weekly orally during weeks 1-3 of a 4-week cycle (day 2, 4, 9, 11, 16, 18; total of 6 doses per 4-week induction cycle). Idarubcin: i.v. infusion, 10 mg/m\^2, on days 1,3,5 in cycle 1. Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m\^2 Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.
Overall Survival	12.6 months Interval 4.2 to Not available due to low number of events	8.0 months Interval 0.89 to Not available due to low number of events

SECONDARY outcome

Timeframe: Time from registration to event, max 2 years

Population: All patients who have received study medication at least once and for whom post-baseline efficacy data upon treatment was available.

Relapse-free survival (RFS) was calculated from the date of CR/CRi until death or relapse, whichever occurred first. Patients were censored on the date of the last follow-up if they were alive without relapse.

Outcome measures

Measure	Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin n=15 Participants Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows: Selinexor: 40 mg/m\^2 twice weekly orally starting on day 2 (total of 8 doses per 4-week induction cycle). Idarubcin: i.v. infusion, 10 mg/m\^2, on days 1,3,5 in cycle 1 Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m\^2 Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.	Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin n=6 Participants Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows: Selinexor: 60 mg flat dose twice weekly orally during weeks 1-3 of a 4-week cycle (day 2, 4, 9, 11, 16, 18; total of 6 doses per 4-week induction cycle). Idarubcin: i.v. infusion, 10 mg/m\^2, on days 1,3,5 in cycle 1. Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m\^2 Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.
Relapse-Free Survival	10.9 months Interval 2.8 to Not available due to low number of events	NA months Interval 4.1 to Not available due to low number of events

SECONDARY outcome

Timeframe: Time from registration to event, max 2 years

Population: All patients who have received study medication at least once and for whom post-baseline efficacy data upon treatment was available.

Event-free survival (EFS) was calculated from the time of informed consent until death, not achieving CR/CRi or relapse after CR/CRi.

Outcome measures

Measure	Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin n=27 Participants Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows: Selinexor: 40 mg/m\^2 twice weekly orally starting on day 2 (total of 8 doses per 4-week induction cycle). Idarubcin: i.v. infusion, 10 mg/m\^2, on days 1,3,5 in cycle 1 Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m\^2 Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.	Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin n=15 Participants Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows: Selinexor: 60 mg flat dose twice weekly orally during weeks 1-3 of a 4-week cycle (day 2, 4, 9, 11, 16, 18; total of 6 doses per 4-week induction cycle). Idarubcin: i.v. infusion, 10 mg/m\^2, on days 1,3,5 in cycle 1. Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m\^2 Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.
Event-Free Survival	5.6 months Interval 2.9 to 12.6	4.3 months Interval 0.9 to 10.4

SECONDARY outcome

Timeframe: Time from registration to event, max 2 years

Population: All patients who have received study medication at least once and for whom post-baseline efficacy data upon treatment was available.

Progression-free survival (PFS) was calculated from the time of informed consent to the date of recurrence or death, whichever occurred first. Patients were censored at the date of the last follow-up visit if they were alive without relapse.

Disease progression was defined as presence of >50% increase in bone marrow blasts to a level of at least 50% and/or a doubling of the percentage of peripheral blood blasts to a level of at least 50%.

Outcome measures

Measure	Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin n=27 Participants Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows: Selinexor: 40 mg/m\^2 twice weekly orally starting on day 2 (total of 8 doses per 4-week induction cycle). Idarubcin: i.v. infusion, 10 mg/m\^2, on days 1,3,5 in cycle 1 Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m\^2 Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.	Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin n=15 Participants Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows: Selinexor: 60 mg flat dose twice weekly orally during weeks 1-3 of a 4-week cycle (day 2, 4, 9, 11, 16, 18; total of 6 doses per 4-week induction cycle). Idarubcin: i.v. infusion, 10 mg/m\^2, on days 1,3,5 in cycle 1. Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m\^2 Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.
Progression-Free Survival	6.3 months Interval 2.3 to 26.3	4.3 months Interval 0.9 to 12.9

Adverse Events

Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin

Serious events: 12 serious events

Other events: 27 other events

Deaths: 16 deaths

Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin

Serious events: 8 serious events

Other events: 15 other events

Deaths: 9 deaths

Serious adverse events

Measure	Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin n=27 participants at risk Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows: Selinexor: 40 mg/m\^2 twice weekly orally starting on day 2 (total of 8 doses per 4-week induction cycle). Idarubcin: i.v. infusion, 10 mg/m\^2, on days 1,3,5 in cycle 1 Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m\^2 Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.	Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin n=15 participants at risk Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows: Selinexor: 60 mg flat dose twice weekly orally during weeks 1-3 of a 4-week cycle (day 2, 4, 9, 11, 16, 18; total of 6 doses per 4-week induction cycle). Idarubcin: i.v. infusion, 10 mg/m\^2, on days 1,3,5 in cycle 1. Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m\^2 Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.
Blood and lymphatic system disorders Febrile neutropenia	3.7% 1/27 • Number of events 3 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	0.00% 0/15 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Blood and lymphatic system disorders Anemia	0.00% 0/27 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	6.7% 1/15 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Blood and lymphatic system disorders Bone marrow hypocellular	0.00% 0/27 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	13.3% 2/15 • Number of events 2 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Cardiac disorders Asystole	0.00% 0/27 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	6.7% 1/15 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Cardiac disorders Atrial fibrillation	3.7% 1/27 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	0.00% 0/15 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Gastrointestinal disorders Diarrhea	3.7% 1/27 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	6.7% 1/15 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Gastrointestinal disorders Colitis	3.7% 1/27 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	0.00% 0/15 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
General disorders Fever	3.7% 1/27 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	0.00% 0/15 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
General disorders General weakness	3.7% 1/27 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	0.00% 0/15 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
General disorders SIRS	3.7% 1/27 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	0.00% 0/15 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Immune system disorders GvHD	3.7% 1/27 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	0.00% 0/15 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Immune system disorders Hemophagocytosis syndrome	0.00% 0/27 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	6.7% 1/15 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Infections and infestations Lung infection	11.1% 3/27 • Number of events 3 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	13.3% 2/15 • Number of events 2 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Infections and infestations Sepsis	3.7% 1/27 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	6.7% 1/15 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Infections and infestations Septic shock	3.7% 1/27 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	0.00% 0/15 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Injury, poisoning and procedural complications Fracture	3.7% 1/27 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	6.7% 1/15 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Investigations Blood bilirubin increased	3.7% 1/27 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	0.00% 0/15 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Investigations Neutrophil count decreased	0.00% 0/27 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	6.7% 1/15 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Nervous system disorders Stroke	3.7% 1/27 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	0.00% 0/15 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Nervous system disorders Subarachnoidal hemorrhage	3.7% 1/27 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	0.00% 0/15 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Vascular disorders Hypotension	3.7% 1/27 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	0.00% 0/15 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.

Other adverse events

Measure	Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin n=27 participants at risk Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows: Selinexor: 40 mg/m\^2 twice weekly orally starting on day 2 (total of 8 doses per 4-week induction cycle). Idarubcin: i.v. infusion, 10 mg/m\^2, on days 1,3,5 in cycle 1 Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m\^2 Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.	Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin n=15 participants at risk Induction cycle: All enrolled patients were treated with selinexor, cytarabine and idarubicin as follows: Selinexor: 60 mg flat dose twice weekly orally during weeks 1-3 of a 4-week cycle (day 2, 4, 9, 11, 16, 18; total of 6 doses per 4-week induction cycle). Idarubcin: i.v. infusion, 10 mg/m\^2, on days 1,3,5 in cycle 1. Cytarabine: continuous i.v. infusion day 1-7, 100 mg/m\^2 Up to two induction cycles were administered. If a second cycle was applied idarubicin was only given on days 1 and 3.
Gastrointestinal disorders Nausea	85.2% 23/27 • Number of events 49 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	86.7% 13/15 • Number of events 19 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Gastrointestinal disorders Diarrhea	88.9% 24/27 • Number of events 99 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	73.3% 11/15 • Number of events 32 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Gastrointestinal disorders Vomiting	81.5% 22/27 • Number of events 46 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	60.0% 9/15 • Number of events 13 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Metabolism and nutrition disorders Anorexia	81.5% 22/27 • Number of events 40 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	53.3% 8/15 • Number of events 10 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Blood and lymphatic system disorders Febrile neutropenia	85.2% 23/27 • Number of events 30 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	33.3% 5/15 • Number of events 27 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
General disorders Fatigue	66.7% 18/27 • Number of events 23 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	60.0% 9/15 • Number of events 15 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Investigations White blood cell decreased	63.0% 17/27 • Number of events 21 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	60.0% 9/15 • Number of events 23 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Investigations Platelet count decreased	70.4% 19/27 • Number of events 33 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	46.7% 7/15 • Number of events 23 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Blood and lymphatic system disorders Anemia	74.1% 20/27 • Number of events 33 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	33.3% 5/15 • Number of events 27 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Metabolism and nutrition disorders Hypokalemia	63.0% 17/27 • Number of events 27 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	13.3% 2/15 • Number of events 2 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Vascular disorders Hypotension	44.4% 12/27 • Number of events 16 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	46.7% 7/15 • Number of events 7 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Investigations Neutrophil count decreased	44.4% 12/27 • Number of events 14 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	40.0% 6/15 • Number of events 15 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Gastrointestinal disorders Mucositis oral	44.4% 12/27 • Number of events 19 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	40.0% 6/15 • Number of events 7 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Respiratory, thoracic and mediastinal disorders Epistaxis	37.0% 10/27 • Number of events 13 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	53.3% 8/15 • Number of events 13 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Nervous system disorders Dizziness	33.3% 9/27 • Number of events 12 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	40.0% 6/15 • Number of events 6 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Gastrointestinal disorders Constipation	25.9% 7/27 • Number of events 8 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	46.7% 7/15 • Number of events 10 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
General disorders Injection site reaction	37.0% 10/27 • Number of events 12 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	20.0% 3/15 • Number of events 5 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Infections and infestations Lung infection	29.6% 8/27 • Number of events 13 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	26.7% 4/15 • Number of events 7 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
General disorders Edema limbs	22.2% 6/27 • Number of events 8 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	33.3% 5/15 • Number of events 6 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Gastrointestinal disorders Abdominal pain	37.0% 10/27 • Number of events 10 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	6.7% 1/15 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Infections and infestations Sepsis	25.9% 7/27 • Number of events 7 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	20.0% 3/15 • Number of events 4 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Psychiatric disorders Depression	18.5% 5/27 • Number of events 5 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	20.0% 3/15 • Number of events 3 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Nervous system disorders Headache	18.5% 5/27 • Number of events 10 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	20.0% 3/15 • Number of events 4 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Metabolism and nutrition disorders Hyponatremia	11.1% 3/27 • Number of events 4 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	26.7% 4/15 • Number of events 6 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Respiratory, thoracic and mediastinal disorders Dyspnea	18.5% 5/27 • Number of events 5 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	13.3% 2/15 • Number of events 2 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Vascular disorders Hematoma	18.5% 5/27 • Number of events 7 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	13.3% 2/15 • Number of events 3 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Psychiatric disorders Insomnia	18.5% 5/27 • Number of events 6 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	13.3% 2/15 • Number of events 2 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
General disorders Fever	7.4% 2/27 • Number of events 2 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	33.3% 5/15 • Number of events 9 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Cardiac disorders Sinus tachycardia	11.1% 3/27 • Number of events 3 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	20.0% 3/15 • Number of events 4 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Nervous system disorders Syncope	18.5% 5/27 • Number of events 5 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	6.7% 1/15 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Investigations Creatinine increased	11.1% 3/27 • Number of events 3 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	13.3% 2/15 • Number of events 2 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Metabolism and nutrition disorders Hyperglycemia	14.8% 4/27 • Number of events 4 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	6.7% 1/15 • Number of events 2 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Metabolism and nutrition disorders Hypocalcemia	14.8% 4/27 • Number of events 5 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	6.7% 1/15 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Infections and infestations Catheter related infection	14.8% 4/27 • Number of events 4 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	6.7% 1/15 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Injury, poisoning and procedural complications Fall	14.8% 4/27 • Number of events 6 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	6.7% 1/15 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Vascular disorders Hypertension	7.4% 2/27 • Number of events 2 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	20.0% 3/15 • Number of events 3 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Skin and subcutaneous tissue disorders Rash maculo-papular	14.8% 4/27 • Number of events 6 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	6.7% 1/15 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Ear and labyrinth disorders Hearing impaired	11.1% 3/27 • Number of events 4 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	6.7% 1/15 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Ear and labyrinth disorders Vertigo	14.8% 4/27 • Number of events 4 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	0.00% 0/15 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Gastrointestinal disorders Stomach pain	11.1% 3/27 • Number of events 3 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	6.7% 1/15 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Gastrointestinal disorders Toothache	14.8% 4/27 • Number of events 5 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	0.00% 0/15 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Immune system disorders Allergic reaction	7.4% 2/27 • Number of events 3 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	13.3% 2/15 • Number of events 2 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Metabolism and nutrition disorders Weight loss	7.4% 2/27 • Number of events 3 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	13.3% 2/15 • Number of events 2 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Metabolism and nutrition disorders Hypomagnesemia	11.1% 3/27 • Number of events 3 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	6.7% 1/15 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Musculoskeletal and connective tissue disorders Pain in extremity	11.1% 3/27 • Number of events 3 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	6.7% 1/15 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Renal and urinary disorders Hematuria	3.7% 1/27 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	20.0% 3/15 • Number of events 3 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Respiratory, thoracic and mediastinal disorders Pleural effusion	11.1% 3/27 • Number of events 3 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	6.7% 1/15 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Cardiac disorders Left ventricular systolic dysfunction	7.4% 2/27 • Number of events 2 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	6.7% 1/15 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Eye disorders Blurred vision	11.1% 3/27 • Number of events 3 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	0.00% 0/15 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Eye disorders Dry eye	7.4% 2/27 • Number of events 2 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	6.7% 1/15 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Gastrointestinal disorders Colitis	11.1% 3/27 • Number of events 3 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	0.00% 0/15 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Gastrointestinal disorders Dysphagia	7.4% 2/27 • Number of events 2 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	6.7% 1/15 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Gastrointestinal disorders Oral hemorrhage	11.1% 3/27 • Number of events 4 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	0.00% 0/15 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
General disorders Edema face	11.1% 3/27 • Number of events 3 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	0.00% 0/15 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Infections and infestations Sinusitis	11.1% 3/27 • Number of events 4 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	0.00% 0/15 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Investigations Weight gain	7.4% 2/27 • Number of events 2 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	6.7% 1/15 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Metabolism and nutrition disorders Hypophosphatemia	11.1% 3/27 • Number of events 4 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	0.00% 0/15 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Musculoskeletal and connective tissue disorders Back pain	7.4% 2/27 • Number of events 2 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	6.7% 1/15 • Number of events 2 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Musculoskeletal and connective tissue disorders Chest wall pain	7.4% 2/27 • Number of events 2 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	6.7% 1/15 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Nervous system disorders Dysgeusia	11.1% 3/27 • Number of events 3 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	0.00% 0/15 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Nervous system disorders Presyncope	7.4% 2/27 • Number of events 2 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	6.7% 1/15 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Renal and urinary disorders Urinary incontinence	7.4% 2/27 • Number of events 2 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	6.7% 1/15 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Respiratory, thoracic and mediastinal disorders Cough	3.7% 1/27 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	13.3% 2/15 • Number of events 2 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Skin and subcutaneous tissue disorders Alopecia	7.4% 2/27 • Number of events 2 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.	6.7% 1/15 • Number of events 1 • Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months. All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.

Additional Information

Dr Anne L. Kranich

GSO mbH

Phone: +494044195460

Email: kranich@gsoglobal.com

Results disclosure agreements

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