Randomized Phase II Study to Assess the Role of Nivolumab as Single Agent to Eliminate Minimal Residual Disease and Maintain Remission in Acute Myelogenous Leukemia (AML) Patients After Chemotherapy (NCI9706 protocol; REMAIN Trial)

Poor- and intermediate-risk AML patients who are not candidates for allogeneic stem cell transplant (SCT) have high risk of disease relapse. Data from pre-clinical studies have suggested potential roles for PD-1/PD-L1 inhibitors in AML. We hypothesized that immunomodulation with checkpoint inhibitors could stimulate anti-leukemia immune response and prevent or delay disease relapse. We conducted a multi-center, open-label, randomized phase II study through NCI CTEP and ETCTN to assess the efficacy of Nivolumab as maintenance therapy for patients with AML in first complete remission (CR) or CR with incomplete hematologic recovery (CRi) who were not candidates for SCT. Patients were enrolled within 60 days after bone marrow biopsy confirming after recovery from final chemotherapy. Patients were stratified and randomized to Observation (Obs) or Nivolumab (3mg/kg IV every 2 weeks for forty-six doses). The primary endpoint was progression-free survival (PFS) defined as time to disease relapse or death due to any reason. Secondary endpoints included overall survival (OS), and evaluation of adverse events following Nivolumab administration. Further exploratory analysis to identify biomarkers of clinical benefit included the measurement of Measurable Residual Disease (MRD) status by ultra-sensitive next generation sequencing (NGS) and RNA profiling of bone marrow samples at the time of randomization.