Nivolumab in Eliminating Minimal Residual Disease and Preventing Relapse in Patients With Acute Myeloid Leukemia in Remission After Chemotherapy
|Adult Acute Myeloid Leukemia in Remission||Other: Clinical Observation Other: Laboratory Biomarker Analysis Biological: Nivolumab||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||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 (Remain Trial)|
- Progression free survival (PFS) [ Time Frame: Time from randomization to disease relapse or death from any cause, assessed up to 2 years post-treatment ]Kaplan-Meier plots will be used to estimate PFS in each arm and a stratified log rank test will be performed to compare the two groups. In addition, Cox proportional hazards models will be fit to provide estimates of the hazard ratio (HR) and associated 95% confidence interval (CIs), both unadjusted and adjusted for baseline covariates. Descriptive, subset analysis of PFS will be performed for MRD positive patients.
- Incidence of adverse effects of nivolumab assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 100 days post-treatment ]Summary tables for AEs will include only AEs that started or worsened after randomization. The incidence of treatment-related adverse events (new or worsening from baseline after randomization) will be summarized by system organ class and/ or preferred term, severity (based on CTCAE grades), type of adverse event, and relation to study treatment by treatment group. Toxicity rates will be compared between the two treatment arms via chi-squares or Fisher's exact tests.
- Non-relapse mortality (NRM) [ Time Frame: Duration between the date of randomization and the date of patient death due to reasons other than relapse, assessed up to 2 years post-treatment ]NRM will be analyzed using competing risks models with deaths due to relapse as a competing risk. Cumulative incidence curves will be generated and treatment effects summarized using the sub-distribution hazard ratio with and without adjustment for covariates
- Overall survival (OS) [ Time Frame: Time from randomization to the date of death from any cause, assessed up to 2 years post-treatment ]For overall survival, Kaplan-Meier plots will be generated for each treatment arm and the curves will be compared using a log rank test. Kaplan-Meier estimates with 95% CI will be summarized every 6 months using Greenwood's formula for the standard error of the Kaplan-Meier estimate. In addition to the Kaplan-Meier estimates, Cox proportional hazards models will be fit to estimate HRs and to assess and adjust for the effects of covariates. Descriptive, subset analysis of OS will be performed for MRD negative patients.
|Actual Study Start Date:||May 27, 2015|
|Estimated Primary Completion Date:||June 28, 2019 (Final data collection date for primary outcome measure)|
Experimental: Arm I (nivolumab)
Patients receive nivolumab IV over 60 minutes once every 2 weeks. Treatment repeats every 2 weeks for 46 courses in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studiesBiological: Nivolumab
Active Comparator: Arm II (observation)
Patients undergo standard of care clinical observation for up to 2 years. Upon disease relapse, patients may cross-over to Arm I.
Other: Clinical Observation
Undergo standard of care clinical observationOther: Laboratory Biomarker Analysis
I. To evaluate and compare the progression free survival rate after randomization in the two treatment arms (nivolumab versus [vs.] observation).
I. To determine and compare the overall survival rates in the two arms. II. To determine and compare the incidence of non-relapse mortality in the two arms.
III. To evaluate the toxicities of nivolumab as maintenance.
I. To analyze programmed cell death (PD)-ligand (L)1 expression on acute myeloid leukemia (AML) cells from peripheral blood and/or bone marrow samples at diagnosis if available and at the time of study enrollment.
II. To monitor AML minimal residual disease (MRD) by Wilms tumor 1 (WT1) polymerase chain reaction (PCR) at enrollment and at subsequent defined time points in the nivolumab-treated and control groups.
III. To perform an exploratory analysis on the frequencies, absolute numbers and subsets of T cells (including regulatory T cells) in the nivolumab-treated and control groups with an emphasis on activation markers.
IV. To perform deep sequencing of T cell receptor (TCR)-alpha and TCR-beta chains on polyclonal T cells at baseline and at subsequent time points in the nivolumab and control groups.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive nivolumab intravenously (IV) over 60 minutes once every 2 weeks. Treatment repeats every 2 weeks for 46 courses in the absence of disease progression or unacceptable toxicity.
ARM II: Patients undergo standard of care clinical observation for up to 2 years. Upon disease relapse, patients may cross-over to Arm I.
After completion of study treatment, patients are followed up for 2 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02275533
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|Principal Investigator:||Hongtao Liu||University of Chicago Comprehensive Cancer Center P2C|