Phase 3
N=472
Efficacy of Oral Azacitidine Plus Best Supportive Care as Maintenance Therapy in Subjects With Acute Myeloid Leukemia (AML) in Complete Remission
Leukemia, Myeloid, Acute
Bottom Line
View on ClinicalTrials.gov: NCT01757535 ↗Enrolled (actual)
472
Serious AEs
46.7%
Results posted
Nov 2020
Primary outcome: Primary: Kaplan-Meier (K-M) Estimate for Overall Survival (OS) — 24.7; 14.8 Months — p=0.0009
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Oral Azacitidine (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 55+ yrs
- Sex
- All
- Sponsor
- Celgene
- Primary completion
- Jul 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Kaplan-Meier (K-M) Estimate for Overall Survival (OS) |
24.7; 14.8 | 0.0009 sig |
| SECONDARY Kaplan-Meier Estimate of Relapse Free Survival (RFS) |
10.2; 4.8 | < 0.0001 sig |
| SECONDARY Kaplan-Meier Estimate of Time to Relapse |
10.2; 4.9 | — |
| SECONDARY Kaplan-Meier Estimates of Time to Discontinuation From Treatment |
14.6; 6.9 | — |
| SECONDARY Number of Participants With Treatment Emergent Adverse Events (TEAEs) |
235; 233; 213; 121; 110; 109 | — |
| SECONDARY Mean Change in the Functional Assessment of Chronic Illness Therapy (FACIT-Fatigue Scale V 4.0) Score From Baseline |
-3.7; -2.5 | — |
| SECONDARY Mean Change in the European Quality of Life-Five Dimensions-Three Levels (EQ-5D-3L) Score From Baseline |
-0.0416; -0.0152 | — |
| SECONDARY Time to Definitive Clinically Meaningful Deterioration for ≥ 2 Consecutive Visits as Measured Using the EQ-5D HRQoL Scale |
NA; NA | 0.7522 |
| SECONDARY Healthcare Resource Utilization (HRU): Rate of Hospital Events Per Person Year |
0.36; 0.63 | — |
| SECONDARY Healthcare Resource Utilization (HRU): Number of Days Hospitalized Per Person-Year |
6.00; 13.13 | — |
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
- Male or female participants ≥ 55 years of age
- Newly diagnosed, histologically confirmed de novo acute myeloid leukemia (AML) or AML secondary to prior myelodysplastic disease or CMML (Chronic myelomonocytic leukemia)
- 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)
- 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:
- 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;
- Participants who have signed the informed consent for the EP of the study;
- Participants who do not meet any of the criteria for study discontinuation
Key Exclusion Criteria
- 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
- Prior bone marrow or stem cell transplantation
- Have achieved CR/CRi following therapy with hypomethylating agents
- Diagnosis of malignant disease within the previous 12 months
- Proven central nervous system (CNS) leukemia
Data sourced from ClinicalTrials.gov (NCT01757535). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.