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

NCT02249091 | Completed Phase 2 Results

• 2 other identifiers: SAIL2014-000526-37
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 3

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)

Outcome Measures

Primary Outcomes (1)

• Number of Participants With CR/CRi = Overall Reponse Rate

  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).

  1-2 induction cycles (4 - 8 weeks)

Secondary Outcomes (7)

• Number of Participants With Partial Remission (PR) = Rate of PR

  1-2 induction cycles (4 - 8 weeks)

• Percentage of Patients Transplanted After Induction Therapy (Stem Cell Transplantation)

  1-2 induction cycles (4 - 8 weeks)

• Early Death Rate

  1 induction cycle (4 weeks)

• Overall Survival

  Time from registration to event, max 2 years

• Relapse-Free Survival

  Time from registration to event, max 2 years

Study Arms (2)

Cohort 1 / Selinexor 40 mg/m^2 in combination with cytarabine and idarubicin

EXPERIMENTAL

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; Drug: Idarubicin; Drug: Cytarabine

Cohort 2 / Selinexor 60 mg flat dose in combination with cytarabine and idarubicin

EXPERIMENTAL

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; Drug: Idarubicin; Drug: Cytarabine

Interventions

Selinexor 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).

Also known as: KPT-330

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

Idarubicin DRUG

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

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

Cytarabine DRUG

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

Also known as: Ara-C

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• GSO Global Clinical Research BV: lead
• Karyopharm Therapeutics Inc: collaborator

Study Sites (3)

Universitätsklinikum Frankfurt

Frankfurt am Main, Hesse, 60590, Germany

Location

Medizinische Hochschule Hannover

Hanover, Lower Saxony, 30625, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Recurrence

Interventions

selinexor; Idarubicin; Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Dr Anne L. Kranich
• Organization: GSO mbH

kranich@gsoglobal.com

+494044195460

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 16, 2014
• First Posted: September 25, 2014
• Study Start: September 1, 2014
• Primary Completion: July 31, 2018
• Study Completion: July 31, 2018
• Last Updated: August 25, 2021
• Results First Posted: August 25, 2021

Record last verified: 2021-08

Locations

DE (3)