Efficacy of Oral Azacitidine Plus Best Supportive Care as Maintenance Therapy in Subjects With Acute Myeloid Leukemia (AML) in Complete Remission

Celgene472 enrolled

Overview

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.

This is an international, multicenter, placebo-controlled, Phase 3 study with a double-blind, randomized, parallel-group design in subjects with de novo AML or AML secondary to prior diagnosis of myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML) aged ≥ 55 years, who are in first CR/CRi following induction therapy with or without consolidation chemotherapy. The study consists of 3 phases; the pre-randomization phase (screening phase), the treatment phase, and the follow-up phase. 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 they meet 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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Eligibility

Sex: ALLMin age: 55 Years

Medical Language ↔ Plain English

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

Locations (223)

Arizona Oncology Associates, P.C.

Phoenix, Arizona, United States

Providence St Joseph Medical Center Cancer Center

Burbank, California, United States

City Of Hope

Duarte, California, United States

University of California San Francisco Fresno Campus

Fresno, California, United States

University of Southern California Norris Cancer Center

Los Angeles, California, United States

Outcomes

Primary Outcomes

Kaplan-Meier (K-M) Estimate for Overall Survival (OS)

Overall survival was defined as time from randomization to death from any cause; participants surviving at the end of the follow-up period, or who withdraw consent, or who were lost to follow up were censored at the date last known alive.

Time frame: Day 1 (randomization) up to data cut off date of 15 July 2019; median follow-up for OS estimated by the reverse K-M method was 41.2 months for all participants.

Secondary Outcomes

Kaplan-Meier Estimate of Relapse Free Survival (RFS)

RFS was defined as the time from the date of randomization to the date of documented relapse or death from any cause, whichever occurred first. Participants who were still alive without documented relapse, or who were lost to follow-up or withdrew consent without documented relapse, were censored at the date of their last bone marrow assessment, prior to receiving any other therapy for AML. Documented relapse was defined as the earliest date of the following: • ≥ 5% bone marrow blasts (myeloblasts) from Central Pathology report, or • appearance of \> 0% blasts in the peripheral blood with a later bone marrow confirmation (bone marrow blast \[myeloblasts\] ≥ 5%) within 100 days, or • at least 2 peripheral blasts ≥ 5% within 30 days.