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

NCT ID: NCT02249091

Last Updated: 2021-08-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-30
• Study Completion Date: 2018-07-31

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.

Conditions

Acute Myeloid Leukemia (Relapsed/Refractory)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

Selinexor

Intervention Type: DRUG

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).

Idarubicin

Intervention Type: DRUG

Infusion, iv, 10 mg/m\^2, on days 1,3,5 in cycle 1, on days 1,3 in cycle 2

Cytarabine

Intervention Type: DRUG

Continuous infusion day 1 to 7, 100 mg/m\^2, iv,

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).

Group Type: EXPERIMENTAL

Selinexor

Intervention Type: DRUG

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).

Idarubicin

Intervention Type: DRUG

Infusion, iv, 10 mg/m\^2, on days 1,3,5 in cycle 1, on days 1,3 in cycle 2

Cytarabine

Intervention Type: DRUG

Continuous infusion day 1 to 7, 100 mg/m\^2, iv,

Interventions

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).

Intervention Type: DRUG

Idarubicin

Infusion, iv, 10 mg/m\^2, on days 1,3,5 in cycle 1, on days 1,3 in cycle 2

Intervention Type: DRUG

Cytarabine

Continuous infusion day 1 to 7, 100 mg/m\^2, iv,

Intervention Type: DRUG

Other Intervention Names

KPT-330; Ara-C

Eligibility Criteria

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:

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

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

3. patients who relapse after conventional chemotherapy or

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

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

4. 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;

5. ECOG performance status ≤ 2

6. 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.

7. Ability to swallow and retain oral medication;

8. Ability to understand and provide signed informed consent;

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

10. 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:

1. Necessity of immunosuppressive drugs

2. GvHD > grade 1

8. 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.

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

10. 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.

11. Clinically significant bleeding within 1 month

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Karyopharm Therapeutics Inc

INDUSTRY

Sponsor Role: collaborator

GSO Global Clinical Research BV

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Universitätsklinikum Frankfurt

Frankfurt am Main, Hesse, Germany

Medizinische Hochschule Hannover

Hanover, Lower Saxony, Germany

Universitätsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Countries

Germany

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2014-000526-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SAIL

Identifier Type: -

Identifier Source: org_study_id