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NCT Number: NCT02249091

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

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.

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Key information

Conditions

Acute Myeloid Leukemia (Relapsed/Refractory) Disease Attributes Hematologic Diseases Hemic and Lymphatic Diseases Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Neoplasms Neoplasms by Histologic Type Pathologic Processes Pathological Conditions, Signs and Symptoms Recurrence

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Universitätsklinikum Frankfurt, Frankfurt am Main, Hesse, Germany

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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).

Other names: KPT-330

Idarubicin

Drug

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

Cytarabine

Drug

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

Other names: Ara-C

Primary outcomes

  1. Number of Participants With CR/CRi = Overall Reponse Rate

    Time frame: 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 outcomes

  1. Number of Participants With Partial Remission (PR) = Rate of PR

    Time frame: 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)

    Time frame: 1-2 induction cycles (4 - 8 weeks)

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

  3. Early Death Rate

    Time frame: 1 induction cycle (4 weeks)

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

  4. Overall Survival

    Time frame: 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 frame: 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 frame: 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 frame: 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%.

Sponsors and collaborators

Lead sponsor

GSO Global Clinical Research BV

Other

Collaborators

  • Karyopharm Therapeutics Inc

Registry information

Official study 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

Important dates

Study start
2014
Primary completion
2018
Study completion
2018
First posted
Sep 25, 2014
Registry last updated
Aug 25, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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