Selinexor (KPT-330) in Older Patients With Relapsed AML
Condition: Acute Myeloid Leukemia (AML)
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: Selinexor; Hydroxyurea; Ara-C
Intervention description: Selinexor oral tablet.; Ara-C Subcutaneous Injection.
Intervention MeSH terms: Cytarabine; Hydroxyurea
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 317.0
Sex: All
Minimum age: 60 Years
Healthy volunteers: No
Keywords: Relapsed/Refractory Acute Myeloid Leukemia; Acute Myeloid Leukemia; AML; Karyopharm; Selinexor; KPT-330

Summary:

      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). Participants 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.
    

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.

          -  Eastern Cooperative Oncology Group (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. Participants 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 participants with malabsorption syndrome, or any other
             disease significantly affecting gastrointestinal function.

          -  Participants whose AML is classified as favorable according to the European
             LeukemiaNet (ELN) disease risk assessment.