In the phase III QUAZAR AML-001 trial, an investigational oral azacitidine therapy, CC-486, induced a statistically significant improvement in overall survival compared with placebo when used as a maintenance therapy in the treatment of patients with newly diagnosed acute myeloid leukemia who achieved a complete response or CR with incomplete blood count recovery following treatment with induction chemotherapy.
Jay Backstrom, MD, MPH
In the phase III QUAZAR AML-001 trial, an investigational oral azacitidine therapy, CC-486, induced a statistically significant improvement in overall survival (OS) compared with placebo when used as a maintenance therapy in the treatment of patients with newly diagnosed acute myeloid leukemia (AML) who achieved a complete response (CR) or CR with incomplete blood count recovery (CRi) following treatment with induction chemotherapy.1Top-line results from the trial announced by Celgene Corporation showed that the study met both its primary and key secondary endpoints.
Regulatory submissions for CC-486 are expected to begin in the first half of 2020, and findings from the QUAZAR AML-001 will be submitted for presentation at a medical meeting.
“AML remains a deadly blood cancer where most patients are not curable and less than 30% of patients survive 5 years,” Jay Backstrom, MD, MPH, chief medical officer for Celgene, said in a press release. “The CC-486 QUAZAR AML-001 study is the first phase III trial to demonstrate that the addition of maintenance therapy has the potential to extend overall survival in a broad population of patients with newly diagnosed AML who have achieved remission with induction chemotherapy.”
CC-486 is a cytidine nucleoside analogue that is thought to lead to DNA hypomethylation and cytotoxicity of hematopoietic cells in the bone marrow causing cell death.
The randomized, double-blind, placebo-controlled trial is exploring the safety and efficacy of CC-486 plus best supportive care as maintenance therapy for patients with AML in first CR/CRi (NCT01757535). The study includes a screening, treatment, and follow-up phase. Additionally, an extension phase was added to the trial for patients who are currently receiving oral azacitidine and demonstrating a clinical benefit to continue to receive treatment until the drug becomes commercially available or the patient meets the criteria for discontinuation. Any patient that discontinued during the treatment phase was followed for survival in the extension phase.
The primary endpoint of the trial is OS and secondary endpoints include relapse-free survival, CR/CRi rate, safety, tolerability, healthcare resource utilization, and patient-reported outcomes.
Patients in the trial were at least 55 years of age, had de novo AML or AML secondary to myelodysplastic syndrome or chronic myelomonocytic leukemia, and had achieved CR/CRi from induction chemotherapy with or without consolidation. Any ECOG performance status from 0 to 3 was allowed. Those who had evidence of translocations, such as t(16;16), were excluded from the trial, along with those who had undergone a prior bone marrow or stem cell transplantation, a malignant disease within the past 12 months, or central nervous system leukemia.
A total of 472 patients were enrolled and randomized 1:1 to receive either 300 mg of oral CC-486 or placebo once daily for 14 days in 28-day cycles until disease progression.
According to initial results, the oral agent was well tolerated and no new safety signals were reported in the phase III trial.
In prior studies of CC-486 in 23 patients with AML, the overall response rate was 48%, which included hematologic improvement in 32% and red blood cell transfusion independence in 20%.2
The most common grade 3/4 adverse events seen with the oral azacitidine agent were febrile neutropenia in 30%, anemia in 22%, neutropenia in 17%, and thrombocytopenia in 17%.