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

• Sponsor: GSO Global Clinical Research BV (Other)
• Overall Status: Completed
• CT.gov ID: NCT02249091
• Collaborator: Karyopharm Therapeutics Inc (Industry)
• Enrollment: 42
• Locations: 3
• Arms: 2
• Duration (Months): 46.9
• Patients Per Site: 14
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

Acute Myeloid Leukemia (AML) is currently treated with chemotherapy by combining several drugs with different ways of inhibiting the cell growth. In this trial, standard chemotherapeutics that have proven their effectiveness for years, Ara-C and Idarubicin, will be combined with a new drug called Selinexor.

Selinexor inhibits the growth of cancer cells by keeping certain proteins in the nucleus which control the cell growth.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia (Relapsed/Refractory)	Drug: Selinexor; Drug: Idarubicin; Drug: Cytarabine	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 42 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: In the initial protocol, 25 patients are included in the clinical trial on the schedule described as cohort 1. After an amendment 15 further patients are included on the schedule described as cohort 2.In the initial protocol, 25 patients are included in the clinical trial on the schedule described as cohort 1. After an amendment 15 further patients are included on the schedule described as cohort 2.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Investigator-Initiated Study To Evaluate Ara-C and Idarubicin in Combination With the Selective Inhibitor Of Nuclear Export (SINE) Selinexor (KPT-330) in Patients With Relapsed Or Refractory AML
• Study Start Date: Sep 1, 2014
• Actual Primary Completion Date: Jul 31, 2018
• Actual Study Completion Date: Jul 31, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 / Selinexor 40 mg/m^2 in combination with cytarabine and idarubicin All enrolled patients are treated with cytarabine at a dose of 100 mg/m² continuous infusion (day 1-7) and idarubicin at a dose of 10 mg/m^2 iv (day 1,3,5) every 4 weeks and selinexor for up to 2 induction cycles. If a second cycle is applied idarubicin is only given on day 1 and 3. Selinexor is administered at a dose of 40 mg/m^2 twice weekly orally starting on day 2 (total of 8 doses per induction cycle).	Drug: Selinexor; Patients receive Selinexor as specified in arm/group description (8 doses of 40 mg/m^2 or 6 doses of 60 mg per induction cycle).; Other Names: KPT-330 ; Drug: Idarubicin; Infusion, iv, 10 mg/m^2, on days 1,3,5 in cycle 1, on days 1,3 in cycle 2; Drug: Cytarabine; Continuous infusion day 1 to 7, 100 mg/m^2, iv,; Other Names: Ara-C
Experimental: Cohort 2 / Selinexor 60 mg flat dose in combination with cytarabine and idarubicin All enrolled patients are treated with cytarabine at a dose of 100 mg/m^2 continuous infusion (day 1-7) and idarubicin at a dose of 10 mg/m^2 iv (day 1,3,5) every 4 weeks and selinexor for up to 2 induction cycles. If a second cycle is applied idarubicin is only given on day 1 and 3. Selinexor is administered at a flat dose of 60 mg twice weekly orally in weeks 1-3 of a 4-week cycle starting on day 2 (total of 6 doses per induction cycle).	Drug: Selinexor; Patients receive Selinexor as specified in arm/group description (8 doses of 40 mg/m^2 or 6 doses of 60 mg per induction cycle).; Other Names: KPT-330 ; Drug: Idarubicin; Infusion, iv, 10 mg/m^2, on days 1,3,5 in cycle 1, on days 1,3 in cycle 2; Drug: Cytarabine; Continuous infusion day 1 to 7, 100 mg/m^2, iv,; Other Names: Ara-C

Outcome Measures

Primary Outcome Measures

1. Number of Participants With CR/CRi = Overall Reponse Rate [1-2 induction cycles (4 - 8 weeks)]

   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).

Secondary Outcome Measures

1. Number of Participants With Partial Remission (PR) = Rate of PR [1-2 induction cycles (4 - 8 weeks)]

   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).

2. Percentage of Patients Transplanted After Induction Therapy (Stem Cell Transplantation) [1-2 induction cycles (4 - 8 weeks)]

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

3. Early Death Rate [1 induction cycle (4 weeks)]

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

4. Overall Survival [Time from registration to event, max 2 years]

   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.

5. Relapse-Free Survival [Time from registration to event, max 2 years]

   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.

6. Event-Free Survival [Time from registration to event, max 2 years]

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

7. Progression-Free Survival [Time from registration to event, max 2 years]

   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%.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Cytological or histological diagnosis of AML with the exception of promyelocytic leukemia (AML M3)

2. Patients must have relapsed/refractory disease (relapse after stem cell transplantation is permitted) as defined as:

3. patients with <PR after first cycle of induction chemotherapy, or

4. patients with <CR(i) after second cycle of induction chemotherapy, or

5. patients who relapse after conventional chemotherapy or

6. patients who have undergone a single stem cell transplantation and who have relapse of their AML.

7. Men and women aged ≥18 years and eligible for standard dose of chemotherapy (7+3);

8. A period of at least 3 weeks needs to have elapsed since last treatment (with the exception of hydroxyurea) before participating in this study. Hydroxyurea induction therapy to reduce peripheral blast counts is permitted prior to initiation of treatment on protocol. Treatment may begin in <3 weeks from last treatment if deemed in the best interest of the patient after discussion with the PI of the study;

9. ECOG performance status ≤ 2

10. Serum biochemical values with the following limits unless considered due to leukemia: creatinine ≤2 mg/dl; total bilirubin ≤2x ULN, unless increase is due to hemolysis or congenital disorder; transaminases (SGPT or SGOT) ≤2.5x ULN.

11. Ability to swallow and retain oral medication;

12. Ability to understand and provide signed informed consent;

13. Cardiac ejection fraction must be >/=50% (by echocardiography).

14. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

Exclusion Criteria:

1. Treatment with any investigational agent within four weeks.

2. Cumulative anthracycline dose (daunorubicin or equivalent) >360 mg/m^2

3. HIV infection

4. Presence of any medical or psychiatric condition which may limit full compliance with the study, including but not limited to:

5. Presence of CNS leukemia

6. Unresolved toxicity from previous anti-cancer therapy or incomplete recovery from surgery.

7. For patients after SCT as part of prior treatment:

8. Necessity of immunosuppressive drugs

9. GvHD > grade 1

10. Any of the following within the 12 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or other thromboembolic event.

11. Ongoing cardiac dysrhythmias of NCI CTCAE >/= Grade 2.

12. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study.

13. Clinically significant bleeding within 1 month

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Universitätsklinikum Frankfurt	Frankfurt am Main	Hessen	Germany	60590
2	Medizinische Hochschule Hannover	Hannover	Niedersachsen	Germany	30625
3	Universitätsklinikum Hamburg-Eppendorf	Hamburg		Germany	20246

Sponsors and Collaborators

• GSO Global Clinical Research BV
• Karyopharm Therapeutics Inc

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jan 13, 2017
• Statistical Analysis Plan - Aug 25, 2017

More Information

Publications

None provided.

• Responsible Party: GSO Global Clinical Research BV
• ClinicalTrials.gov Identifier: NCT02249091
• Other Study ID Numbers: SAIL; 2014-000526-37
• First Posted: Sep 25, 2014
• Last Update Posted: Aug 25, 2021
• Last Verified: Aug 1, 2021

• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Cytarabine; Idarubicin

Study Results

Participant Flow

Recruitment Details	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).

Arm/Group Title	Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin	Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	27	15
COMPLETED	7	2
NOT COMPLETED	20	13

Baseline Characteristics

Arm/Group Title	Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin	Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin	Total
Arm/Group Description	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.	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 of all reporting groups
Overall Participants	27	15	42
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.0 (15.18)	58.5 (13.55)	55.6 (14.62)
Sex: Female, Male (Count of Participants)
Female	11 40.7%	6 40%	17 40.5%
Male	16 59.3%	9 60%	25 59.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 6.7%	1 2.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	27 100%	14 93.3%	41 97.6%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Germany	27 100%	15 100%	42 100%
Leukemia diagnosis (Count of Participants)
De Novo Acute Myeloid Leukemia (AML)	19 70.4%	12 80%	31 73.8%
Therapy-induced AML	2 7.4%	0 0%	2 4.8%
Secondary AML	6 22.2%	3 20%	9 21.4%
Prior stem cell transplantation (SCT) (Count of Participants)
Count of Participants [Participants]	10 37%	7 46.7%	17 40.5%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With CR/CRi = Overall Reponse Rate
Description	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).
Time Frame	1-2 induction cycles (4 - 8 weeks)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin	Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin
Arm/Group Description	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.	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.
Measure Participants	27	15
Count of Participants [Participants]	15 55.6%	6 40%

2. Secondary Outcome

Title	Number of Participants With Partial Remission (PR) = Rate of PR
Description	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).
Time Frame	1-2 induction cycles (4 - 8 weeks)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin	Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin
Arm/Group Description	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.	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.
Measure Participants	27	15
Count of Participants [Participants]	0 0%	0 0%

3. Secondary Outcome

Title	Percentage of Patients Transplanted After Induction Therapy (Stem Cell Transplantation)
Description	Percentage of patients being transplanted after induction therapy (stem cell transplantation)
Time Frame	1-2 induction cycles (4 - 8 weeks)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin	Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin
Arm/Group Description	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.	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.
Measure Participants	27	15
Count of Participants [Participants]	11 40.7%	4 26.7%

4. Secondary Outcome

Title	Early Death Rate
Description	Early death was defined as death before the end of the first induction cycle.
Time Frame	1 induction cycle (4 weeks)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin	Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin
Arm/Group Description	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.	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.
Measure Participants	27	15
Count of Participants [Participants]	0 0%	4 26.7%

5. Secondary Outcome

Title	Overall Survival
Description	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.
Time Frame	Time from registration to event, max 2 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin	Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin
Arm/Group Description	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.	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.
Measure Participants	27	15
Median (95% Confidence Interval) [months]	12.6	8.0

6. Secondary Outcome

Title	Relapse-Free Survival
Description	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.
Time Frame	Time from registration to event, max 2 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin	Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin
Arm/Group Description	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.	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.
Measure Participants	15	6
Median (95% Confidence Interval) [months]	10.9	NA

7. Secondary Outcome

Title	Event-Free Survival
Description	Event-free survival (EFS) was calculated from the time of informed consent until death, not achieving CR/CRi or relapse after CR/CRi.
Time Frame	Time from registration to event, max 2 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin	Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin
Arm/Group Description	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.	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.
Measure Participants	27	15
Median (95% Confidence Interval) [months]	5.6	4.3

8. Secondary Outcome

Title	Progression-Free Survival
Description	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%.
Time Frame	Time from registration to event, max 2 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin	Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin
Arm/Group Description	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.	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.
Measure Participants	27	15
Median (95% Confidence Interval) [months]	6.3	4.3

Adverse Events

Time Frame	Throughout the treatment period from start of treatment until one month after the last dose of study mediation, on average 2 months.
Adverse Event Reporting Description	All patients taking at least one dose of study medication were included in the safety population. This applied to all 42 patients included.
Arm/Group Title	Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin		Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin
Arm/Group Description	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.		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.
All Cause Mortality
	Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin		Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/27 (59.3%)		9/15 (60%)
Serious Adverse Events
	Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin		Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/27 (44.4%)		8/15 (53.3%)
Blood and lymphatic system disorders
Febrile neutropenia	1/27 (3.7%)	3	0/15 (0%)	0
Anemia	0/27 (0%)	0	1/15 (6.7%)	1
Bone marrow hypocellular	0/27 (0%)	0	2/15 (13.3%)	2
Cardiac disorders
Asystole	0/27 (0%)	0	1/15 (6.7%)	1
Atrial fibrillation	1/27 (3.7%)	1	0/15 (0%)	0
Gastrointestinal disorders
Diarrhea	1/27 (3.7%)	1	1/15 (6.7%)	1
Colitis	1/27 (3.7%)	1	0/15 (0%)	0
General disorders
Fever	1/27 (3.7%)	1	0/15 (0%)	0
General weakness	1/27 (3.7%)	1	0/15 (0%)	0
SIRS	1/27 (3.7%)	1	0/15 (0%)	0
Immune system disorders
GvHD	1/27 (3.7%)	1	0/15 (0%)	0
Hemophagocytosis syndrome	0/27 (0%)	0	1/15 (6.7%)	1
Infections and infestations
Lung infection	3/27 (11.1%)	3	2/15 (13.3%)	2
Sepsis	1/27 (3.7%)	1	1/15 (6.7%)	1
Septic shock	1/27 (3.7%)	1	0/15 (0%)	0
Injury, poisoning and procedural complications
Fracture	1/27 (3.7%)	1	1/15 (6.7%)	1
Investigations
Blood bilirubin increased	1/27 (3.7%)	1	0/15 (0%)	0
Neutrophil count decreased	0/27 (0%)	0	1/15 (6.7%)	1
Nervous system disorders
Stroke	1/27 (3.7%)	1	0/15 (0%)	0
Subarachnoidal hemorrhage	1/27 (3.7%)	1	0/15 (0%)	0
Vascular disorders
Hypotension	1/27 (3.7%)	1	0/15 (0%)	0
Other (Not Including Serious) Adverse Events
	Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin		Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	27/27 (100%)		15/15 (100%)
Blood and lymphatic system disorders
Febrile neutropenia	23/27 (85.2%)	30	5/15 (33.3%)	27
Anemia	20/27 (74.1%)	33	5/15 (33.3%)	27
Cardiac disorders
Sinus tachycardia	3/27 (11.1%)	3	3/15 (20%)	4
Left ventricular systolic dysfunction	2/27 (7.4%)	2	1/15 (6.7%)	1
Ear and labyrinth disorders
Hearing impaired	3/27 (11.1%)	4	1/15 (6.7%)	1
Vertigo	4/27 (14.8%)	4	0/15 (0%)	0
Eye disorders
Blurred vision	3/27 (11.1%)	3	0/15 (0%)	0
Dry eye	2/27 (7.4%)	2	1/15 (6.7%)	1
Gastrointestinal disorders
Nausea	23/27 (85.2%)	49	13/15 (86.7%)	19
Diarrhea	24/27 (88.9%)	99	11/15 (73.3%)	32
Vomiting	22/27 (81.5%)	46	9/15 (60%)	13
Mucositis oral	12/27 (44.4%)	19	6/15 (40%)	7
Constipation	7/27 (25.9%)	8	7/15 (46.7%)	10
Abdominal pain	10/27 (37%)	10	1/15 (6.7%)	1
Stomach pain	3/27 (11.1%)	3	1/15 (6.7%)	1
Toothache	4/27 (14.8%)	5	0/15 (0%)	0
Colitis	3/27 (11.1%)	3	0/15 (0%)	0
Dysphagia	2/27 (7.4%)	2	1/15 (6.7%)	1
Oral hemorrhage	3/27 (11.1%)	4	0/15 (0%)	0
General disorders
Fatigue	18/27 (66.7%)	23	9/15 (60%)	15
Injection site reaction	10/27 (37%)	12	3/15 (20%)	5
Edema limbs	6/27 (22.2%)	8	5/15 (33.3%)	6
Fever	2/27 (7.4%)	2	5/15 (33.3%)	9
Edema face	3/27 (11.1%)	3	0/15 (0%)	0
Immune system disorders
Allergic reaction	2/27 (7.4%)	3	2/15 (13.3%)	2
Infections and infestations
Lung infection	8/27 (29.6%)	13	4/15 (26.7%)	7
Sepsis	7/27 (25.9%)	7	3/15 (20%)	4
Catheter related infection	4/27 (14.8%)	4	1/15 (6.7%)	1
Sinusitis	3/27 (11.1%)	4	0/15 (0%)	0
Injury, poisoning and procedural complications
Fall	4/27 (14.8%)	6	1/15 (6.7%)	1
Investigations
White blood cell decreased	17/27 (63%)	21	9/15 (60%)	23
Platelet count decreased	19/27 (70.4%)	33	7/15 (46.7%)	23
Neutrophil count decreased	12/27 (44.4%)	14	6/15 (40%)	15
Creatinine increased	3/27 (11.1%)	3	2/15 (13.3%)	2
Weight gain	2/27 (7.4%)	2	1/15 (6.7%)	1
Metabolism and nutrition disorders
Anorexia	22/27 (81.5%)	40	8/15 (53.3%)	10
Hypokalemia	17/27 (63%)	27	2/15 (13.3%)	2
Hyponatremia	3/27 (11.1%)	4	4/15 (26.7%)	6
Hyperglycemia	4/27 (14.8%)	4	1/15 (6.7%)	2
Hypocalcemia	4/27 (14.8%)	5	1/15 (6.7%)	1
Weight loss	2/27 (7.4%)	3	2/15 (13.3%)	2
Hypomagnesemia	3/27 (11.1%)	3	1/15 (6.7%)	1
Hypophosphatemia	3/27 (11.1%)	4	0/15 (0%)	0
Musculoskeletal and connective tissue disorders
Pain in extremity	3/27 (11.1%)	3	1/15 (6.7%)	1
Back pain	2/27 (7.4%)	2	1/15 (6.7%)	2
Chest wall pain	2/27 (7.4%)	2	1/15 (6.7%)	1
Nervous system disorders
Dizziness	9/27 (33.3%)	12	6/15 (40%)	6
Headache	5/27 (18.5%)	10	3/15 (20%)	4
Syncope	5/27 (18.5%)	5	1/15 (6.7%)	1
Dysgeusia	3/27 (11.1%)	3	0/15 (0%)	0
Presyncope	2/27 (7.4%)	2	1/15 (6.7%)	1
Psychiatric disorders
Depression	5/27 (18.5%)	5	3/15 (20%)	3
Insomnia	5/27 (18.5%)	6	2/15 (13.3%)	2
Renal and urinary disorders
Hematuria	1/27 (3.7%)	1	3/15 (20%)	3
Urinary incontinence	2/27 (7.4%)	2	1/15 (6.7%)	1
Respiratory, thoracic and mediastinal disorders
Epistaxis	10/27 (37%)	13	8/15 (53.3%)	13
Dyspnea	5/27 (18.5%)	5	2/15 (13.3%)	2
Pleural effusion	3/27 (11.1%)	3	1/15 (6.7%)	1
Cough	1/27 (3.7%)	1	2/15 (13.3%)	2
Skin and subcutaneous tissue disorders
Rash maculo-papular	4/27 (14.8%)	6	1/15 (6.7%)	1
Alopecia	2/27 (7.4%)	2	1/15 (6.7%)	1
Vascular disorders
Hypotension	12/27 (44.4%)	16	7/15 (46.7%)	7
Hematoma	5/27 (18.5%)	7	2/15 (13.3%)	3
Hypertension	2/27 (7.4%)	2	3/15 (20%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.