Clinical Trials /

Selinexor (KPT-330) in Older Patients With Relapsed AML

NCT02088541

Description:

This is a randomized, multicenter, open-label, phase 2 study of the SINE compound, selinexor given orally versus specified investigator choices (one of three potential salvage therapies). Patients age ≥ 60 years with relapsed or refractory AML of any type except for AML M3, after one prior therapy only, who have never undergone and who are not currently eligible for stem cell transplantation and are currently deemed unfit for intensive chemotherapy.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Selinexor (KPT-330) in Older Patients With Relapsed AML
  • Official Title: A Randomized, Open Label, Phase 2 Study of the Selective Inhibitor of Nuclear Export (Sine) Selinexor (KPT-330) Versus Specified Physician's Choice in Patients ≥ 60 Years Old With Relapsed or Refractory Acute Myeloid Leukemia (AML) Who Are Ineligible for Intensive Chemotherapy and/or Transplantation

Clinical Trial IDs

  • ORG STUDY ID: KCP-330-008
  • NCT ID: NCT02088541

Conditions

  • Acute Myeloid Leukemia (AML)

Interventions

DrugSynonymsArms
SelinexorKPT-330Selinexor (KPT-330)
HydroxyureaHydroxycarbamidePhysician's Choice
Ara-CCytarabine, Cytosine arabinoside, Cytosar-U, DepocytPhysician's Choice
Azacitidine5-azacytidine, VidazaPhysician's Choice
DecitabineDacogen, 5-aza-2'-deoxycytidine,Physician's Choice

Purpose

This is a randomized, multicenter, open-label, phase 2 study of the SINE compound, selinexor given orally versus specified investigator choices (one of three potential salvage therapies). Patients age ≥ 60 years with relapsed or refractory AML of any type except for AML M3, after one prior therapy only, who have never undergone and who are not currently eligible for stem cell transplantation and are currently deemed unfit for intensive chemotherapy.

Detailed Description

      This is a randomized, multicenter, open-label phase 2 study of the SINE compound, selinexor
      given orally versus restricted investigator choice (i.e., one of three potential salvage
      therapies).

      Patients who have never been transplant eligible, are currently deemed unfit for intensive
      chemotherapy, ≥ 60 years old, who have AML (except Acute Promyelocytic Leukemia: APL, AML M3)
      after one prior treatment of either hypomethylating agent or a regimen including Ara-C, and
      are meeting the inclusion and exclusion criteria will be randomized to receive either oral
      selinexor or physician's choice (one of three potential treatments: best supportive care
      (BSC) alone, or BSC + hypomethylating agent, or BSC + low dose Ara-C until disease
      progression, death or intolerance has occurred.
    

Trial Arms

NameTypeDescriptionInterventions
Selinexor (KPT-330)Experimental60 mg twice weekly (Protocol Versions ≥ 5.0); ~55 mg/m² dose, based on patient's BSA, twice weekly (Protocol Versions < 5.0).
  • Selinexor
Physician's ChoiceActive ComparatorOne of the following 3 conventional care regimens will be selected by the physician: Best supportive care (BSC) including blood product transfusions, antimicrobials, growth factors as needed, and hydroxyurea; BSC + low dose Ara-C, 20 mg bid by subcutaneous (sc) injection daily on Days 1-10/14 days (20/28 doses) to be repeated at 28 to 42 day intervals; BSC + hypomethylating agent: azacitidine 75 mg/m² by sc injection daily on Days 1-7, (or Days 1-5 and 8-9 under Protocol Versions ≥ 5.0), for a total of 7 doses, to be repeated at ≥ 28 day intervals; or decitabine (20 mg/m² IV over 1 hour daily on Days 1-5 (or Days 1-10 under Protocol Versions ≥ 5.0), to be repeated at ≥ 28 day intervals).
  • Hydroxyurea
  • Ara-C
  • Azacitidine
  • Decitabine

Eligibility Criteria

        Inclusion Criteria:

          -  Age ≥ 60 years with relapsed or refractory AML of any type except for acute
             promyelocytic leukemia (APL; AML M3), after at least 1 prior AML therapy , who have
             never undergone, and who are not currently eligible for, stem cell transplantation,
             and are currently deemed unfit for intensive chemotherapy.

          -  ECOG ≤ 2.

          -  Must have available archival or recently acquired bone marrow biopsy/aspiration or
             tumor tissue for central review to be eligible.

          -  Relapsed or refractory AML, defined as either: recurrence of disease after a complete
             remission (CR), or failure to achieve CR with initial therapy.

          -  Must have received at least 1 prior line of AML therapy given at standard doses and
             must have progressed after their most recent therapy. Prior therapy must have
             included: a hypomethylating agent with at least 2 cycles.

          -  At least 2 weeks must have elapsed since the last anti-leukemia treatment (with the
             exception of hydroxyurea) before first dose in this study.

        Exclusion Criteria:

          -  Treatment with any investigational agent within 3 weeks prior to first dose in this
             study.

          -  Presence of central nervous system (CNS) leukemia.

          -  In blast transformation of chronic myeloid leukemia (CML). Prior myelodysplastic
             syndrome (MDS) is acceptable; prior treatment for MDS does not count as an AML
             therapy.

          -  Major surgery within 2 weeks of first dose of study drug. Patients must have recovered
             from the effects of any surgery performed greater than 2 weeks previously.

          -  Concurrent active malignancy under treatment.

          -  Known active hepatitis B virus (HBV) or C virus (HCV) infection; or known to be
             positive for HCV ribonucleic acid (RNA) or HBsAg (HBV surface antigen).

          -  Known HIV infection.

          -  Unable to swallow tablets, or patients with malabsorption syndrome, or any other
             disease significantly affecting gastrointestinal function.

          -  Patients whose AML is classified as favorable according to the European LeukemiaNet
             (ELN) disease risk assessment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:60 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall survival
Time Frame:From the date of randomization until the date of death, or study end (up to approximately 104 weeks)
Safety Issue:
Description:To determine overall survival (OS) of Selinexor as compared to physician choice (PC).

Secondary Outcome Measures

Measure:3 month survival
Time Frame:up to 3 months
Safety Issue:
Description:Survival at 3 months post-randomization

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Karyopharm Therapeutics Inc

Trial Keywords

  • Relapsed/Refractory Acute Myeloid Leukemia
  • Acute Myeloid Leukemia
  • AML
  • Karyopharm
  • Selinexor
  • KPT-330

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