Efficacy of Oral Azacitidine Plus Best Supportive Care as Maintenance Therapy in Subjects With Acute Myeloid Leukemia (AML) in Complete Remission
Condition: Leukemia, Myeloid, Acute
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: Oral Azacitidine; Placebo
Intervention description: 300 mg oral azacitidine on days 1 to 14 of each 28-day treatment cycle.; Identically matching placebo tablets on days 1 to 14 of each 28-day treatment cycle.
Intervention MeSH terms: Azacitidine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 472.0
Sex: All
Minimum age: 55 Years
Healthy volunteers: No
Keywords: Maintenance therapy; AML; Acute Myeloid Leukemia; Oral Azacitidine; Best supportive care; Complete remission

Summary:

      This study enrolled 472 participants, aged 55 or older, with a diagnosis of de novo acute
      myeloid leukemia (AML) or AML secondary to prior myelodysplastic disease or chronic
      myelomonocytic leukemia (CMML), and who have achieved first complete remission (CR)/ complete
      remission with incomplete blood count recovery (CRi) following induction with or without
      consolidation chemotherapy.

      The study is amended to include an extension phase (EP). The EP allows participants who are
      currently receiving oral azacitidine and who are demonstrating clinical benefit as assessed
      by the investigator, to continue receiving oral azacitidine after unblinding by sponsor until
      the participant meets the criteria for study discontinuation or until oral azacitidine
      becomes commercially available and reimbursed. In addition, all participants in the placebo
      arm and participants who had been discontinued from the treatment phase (irrespective of
      randomization arm) and continuing in the follow-up phase will be followed for survival in the
      EP.
    

Eligibility criteria:

        Key Inclusion Criteria:

          1. Male or female participants ≥ 55 years of age

          2. Newly diagnosed, histologically confirmed de novo acute myeloid leukemia (AML) or AML
             secondary to prior myelodysplastic disease or CMML (Chronic myelomonocytic leukemia)

          3. First complete remission (CR)/ complete remission with incomplete blood count recovery
             (CRi) with induction therapy with intensive chemotherapy with or without consolidation
             therapy within 4 months (+/- 7 days of achieving CR or CRi)

          4. Eastern Cooperative Oncology Group (ECOG) performance status - 0, 1, 2, 3

        Key Inclusion Criteria in the Extended Phase of the study:

        At the Investigator's discretion and with approval of the sponsor, participants meeting all
        of the following eligibility criteria are eligible to enter the extension phase:

          1. All participants randomized into the oral azacitidine or placebo arm and are
             continuing in either the treatment phase or follow-up phase of the CC-486-AML-001
             study;

               -  Participants randomized to oral azacitidine treatment arm and continuing in the
                  treatment phase demonstrating clinical benefit as assessed by the investigator
                  are eligible to receive oral azacitidine in the extension phase (EP);

               -  Participants randomized into placebo arm of the study will not receive oral
                  azacitidine in the EP, but will be followed for survival in the EP;

               -  Participants currently in the follow-up phase will continue to be followed for
                  survival in the EP;

          2. Participants who have signed the informed consent for the EP of the study;

          3. Participants who do not meet any of the criteria for study discontinuation

        Key Exclusion Criteria:

          1. AML with inversion (inv)(16), translocation = t(8;21), t(16;16), t(15;17), or t(9;22)
             or molecular evidence of such translocations

          2. Prior bone marrow or stem cell transplantation

          3. Have achieved CR/CRi following therapy with hypomethylating agents

          4. Diagnosis of malignant disease within the previous 12 months

          5. Proven central nervous system (CNS) leukemia