A Phase II Study of Selinexor Plus Cytarabine and Idarubicin in Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML)
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 |
---|---|---|
Phase 2 |
Study Design
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:
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:
|
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:
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:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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).
- 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)
- Early Death Rate [1 induction cycle (4 weeks)]
Early death was defined as death before the end of the first induction cycle.
- 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.
- 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.
- 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.
- 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
Inclusion Criteria:
-
Cytological or histological diagnosis of AML with the exception of promyelocytic leukemia (AML M3)
-
Patients must have relapsed/refractory disease (relapse after stem cell transplantation is permitted) as defined as:
-
patients with <PR after first cycle of induction chemotherapy, or
-
patients with <CR(i) after second cycle of induction chemotherapy, or
-
patients who relapse after conventional chemotherapy or
-
patients who have undergone a single stem cell transplantation and who have relapse of their AML.
-
Men and women aged ≥18 years and eligible for standard dose of chemotherapy (7+3);
-
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;
-
ECOG performance status ≤ 2
-
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.
-
Ability to swallow and retain oral medication;
-
Ability to understand and provide signed informed consent;
-
Cardiac ejection fraction must be >/=50% (by echocardiography).
-
Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
Exclusion Criteria:
-
Treatment with any investigational agent within four weeks.
-
Cumulative anthracycline dose (daunorubicin or equivalent) >360 mg/m^2
-
HIV infection
-
Presence of any medical or psychiatric condition which may limit full compliance with the study, including but not limited to:
-
Presence of CNS leukemia
-
Unresolved toxicity from previous anti-cancer therapy or incomplete recovery from surgery.
-
For patients after SCT as part of prior treatment:
-
Necessity of immunosuppressive drugs
-
GvHD > grade 1
-
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.
-
Ongoing cardiac dysrhythmias of NCI CTCAE >/= Grade 2.
-
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.
-
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)
More Information
Publications
None provided.- SAIL
- 2014-000526-37
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). |
---|---|
Pre-assignment Detail |
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
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%
|
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%
|
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%
|
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%
|
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
|
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
|
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
|
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
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.
Results Point of Contact
Name/Title | Dr Anne L. Kranich |
---|---|
Organization | GSO mbH |
Phone | +494044195460 |
kranich@gsoglobal.com |
- SAIL
- 2014-000526-37