A Study of Idasanutlin With Cytarabine Versus Cytarabine Plus Placebo in Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML)
Condition: Leukemia, Myeloid, Acute
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: Cytarabine; Idasanutlin; Placebo
Intervention description: Participants will receive cytarabine 1 gram per square meter (g/m^2) intravenous (IV) infusion for 5 days of every treatment cycle.; Participants will receive idasanutlin 300 mg per oral (PO) twice daily (BID) (in Cycle 1) or once daily (QD) (in Cycles 2 and 3) for 5 days of every treatment cycle.; Participants will receive idasanutlin matching placebo PO BID or QD for 5 days of every treatment cycle.
Intervention MeSH terms: Cytarabine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 447.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a multicenter, double-blind, randomized, placebo-controlled study designed to compare
      overall survival in participants with relapsed or refractory AML treated with idasanutlin in
      combination with cytarabine versus participants treated with placebo and cytarabine.
      Participants will receive induction treatment with idasanutlin/placebo and cytarabine (Cycle
      1). Responding participants may continue to receive a maximum of further two cycles of
      consolidation (Cycle 2 and Cycle 3). Complete remission (CR), CR with incomplete platelet
      count recovery (CRp), overall remission rate (ORR), event-free survival (EFS) and percentage
      of participants with an allogeneic hematopoietic stem cell transplant (HSCT) will also be
      compared between treatment arms. This study will include participants with and without TP53
      wild type (TP53 WT) mutations.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Documented/confirmed first/second refractory/relapsed AML using World Health
             Organization classification, except acute promyelocytic leukemia

          -  No more than 2 prior induction regimens (excluding prior HSCT) in their first line
             treatment and one must have included cytarabine with an anthracycline (or
             anthracenedione)

          -  Eastern Cooperative Oncology Group performance status of 0 to 2

          -  Adequate hepatic and renal function

          -  White blood cell (WBC) count at randomization less than or equal to (</=) 50000 cells
             per cubic millimeter (/mm^3)

        Exclusion Criteria:

          -  First relapsed participants aged less than (<) 60 years with first CR duration greater
             than (>) 1 year

          -  Participants with prior documented antecedent hematological disorder (AHD)

          -  AML secondary to any prior chemotherapy unrelated to leukemia

          -  Participants who are either refractory to or relapsed within 90 days of receiving a
             regimen containing a cumulative dose of greater than or equal to (>/=) 18 g/m^2 of
             cytarabine

          -  Participants who have received allogeneic HSCT within 90 days prior to randomization

          -  Participants who have received immunosuppressive therapy for graft versus host disease
             or for engraftment syndrome after autologous stem cell transplantation within 2 weeks
             prior to randomization

          -  Prior treatment with an Murine Double Minute 2 (MDM2) antagonist

          -  Participants receiving any other investigational or commercial agents or therapies
             administered with the intention to treat their malignancy within 30 days from first
             receipt of study drug

          -  Participants with a history of other malignancy within 5 years prior to screening
             except for malignancy that has been in remission without treatment for at least 2
             years prior to randomization

          -  Participants who have any severe and/or uncontrolled medical conditions or other
             conditions that could affect their participation in the study

          -  Participants with extramedullary AML with no evidence of systemic involvement

          -  Pregnant or breastfeeding participants