Design of the randomized, Phase III, QUAZAR AML Maintenance trial of CC-486 (oral azacitidine) maintenance therapy in acute myeloid leukemia

Gail J Roboz, Pau Montesinos, Dominik Selleslag, Andrew Wei, Jun-Ho Jang, Jose Falantes, Maria T Voso, Hamid Sayar, Kimmo Porkka, Paula Marlton, Antonio Almeida, Sanjay Mohan, Farhad Ravandi, Guillermo Garcia-Manero, Barry Skikne, Hagop Kantarjian, Gail J Roboz, Pau Montesinos, Dominik Selleslag, Andrew Wei, Jun-Ho Jang, Jose Falantes, Maria T Voso, Hamid Sayar, Kimmo Porkka, Paula Marlton, Antonio Almeida, Sanjay Mohan, Farhad Ravandi, Guillermo Garcia-Manero, Barry Skikne, Hagop Kantarjian

Abstract

Older patients with acute myeloid leukemia (AML) have worse rates of complete remission and shorter overall survival than younger patients. The epigenetic modifier CC-486 is an oral formulation of azacitidine with promising clinical activity in patients with AML in Phase I studies. The Phase III, randomized, double-blind, placebo-controlled QUAZAR AML Maintenance trial (CC-486-AML-001) examines CC-486 maintenance therapy (300 mg/day for 14 days of 28-day treatment cycles) for patients aged ≥55 years with AML in first complete remission. The primary end point is overall survival. Secondary end points include relapse-free survival, safety, health-related quality of life and healthcare resource utilization. This trial will investigate whether CC-486 maintenance can prolong remission and improve survival for older patients with AML.

Trial registration: ClinicalTrials.gov NCT01757535.

Keywords: CC-486; Phase III; acute myeloid leukemia; de novo; elderly; maintenance therapy; oral azacitidine; secondary.

Conflict of interest statement

Financial & competing interests disclosure

The CC-486-AML-001 trial is sponsored by Celgene Corporation. GJ Roboz’ institution received a grant from Celgene Corporation. PM Fernandes’ institution received a grant from Celgene Corporation. A Wei received a grant from Celgene Corporation. MT Voso received support for travel to the meeting for the study or other purposes from Celgene Corporation. F Ravandi-Kashani's institution received a grant from Celgene Corporation. B Skikne is employed by Celgene Corporation in which he has an equity interest. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Medical writing assistance was provided by J Leslie of MediTech Media and was funded by Celgene Corporation.

Figures

Figure 1. . Study schema of the…
Figure 1.. Study schema of the CC-486-AML-001 trial.
†May also discontinue treatment based on investigator's decision. AML: Acute myeloid leukemia; BM: Bone marrow; CR: Complete remission; CRi: Complete remission with incomplete blood count recovery.
Figure 2. . A 90-day randomization window.
Figure 2.. A 90-day randomization window.
Only a small proportion of patients with AML are cured (10–15%, dark gray) and relapse (indicated by the dashed line) begins within weeks of achieving complete remission (CR). To avoid enriching for patients with better prognoses who remain in remission longer (shaded portion of the figure), study participants must be enrolled within 90 days of achieving first CR/CR with incomplete blood count recovery. A later enrollment cutoff, for example, beyond 140 days, would include a greater proportion of patients who are likely to be cured long term. This would falsely elevate the number of patients who appear to benefit from the study. The 90-day randomization window provides a more realistic picture of the entire AML population. AML: Acute myeloid leukemia.

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