Phase II Trial of Lymphodepletion and Anti-PD-1 Blockade to Reduce Relapse in High Risk AML Patients Who Are Not Eligible for Allogeneic Stem Cell Transplantation
Overview
- Phase
- Phase 2
- Intervention
- Fludarabine
- Conditions
- Acute Myeloid Leukemia
- Sponsor
- Northside Hospital, Inc.
- Enrollment
- 20
- Locations
- 2
- Primary Endpoint
- Number of Patients With 2-year Relapse Risk
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
AML is the most common acute leukemia in adults. Most patients can undergo allogeneic stem cell transplantation as a possible cure; however, many patients are not candidates for allogeneic transplant due to age, overall health, psychosocial factors, and/or lack of available donors. Therefore, these patients are unable to receive the therapeutic benefits of the "graft-versus-leukemia" effect of donor immune cells. The aim of this study is to hopefully break immune tolerance to AML cells to provide better outcomes in patients with non-favorable risk AML.
Detailed Description
Non-favorable risk AML patients will undergo a preparative regimen of lymphodepletion of Flu/Mel followed by autologous transplantation. Anti-PD-1 therapy of pembrolizumab will begin on Day +1 following stem cell transplantation and will be administered every 3 weeks for a total of 8 doses. According to the literature, the risk of 2-year relapse is estimated to be 60-80% in patients with non-favorable risk AML in CR-1. With this protocol, investigators hypothesize that following lymphodepleting chemotherapy and pembrolizumab, the 2-year relapse risk will decrease to less than or equal to 35%. The one-sided Wald test at 5% significance level will be used to test the hypothesis. The size of 20 patients yields the power of 90.5% assuming that the actual 2-year leukemia-free survival is 60%.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Non-favorable risk AML
- •In CR-1 or subsequent CR
- •Completed at least one cycle of consolidation chemotherapy
- •Collection of at least 2x106/kg CD34+ cells
- •KPS of 70% or greater
Exclusion Criteria
- •Received investigational agent within 4 weeks of first dose
- •Prior chemotherapy, radiation therapy within 2 weeks of first dose
- •Hypersensitivity to pembrolizumab or any of its excipients
- •Received prior therapy with anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Arms & Interventions
Lymphodepletion plus Pembrolizumab
Fludarabine \& Melphalan followed by autologous stem cell transplantation. Pembrolizumab will begin on Day +1.
Intervention: Fludarabine
Lymphodepletion plus Pembrolizumab
Fludarabine \& Melphalan followed by autologous stem cell transplantation. Pembrolizumab will begin on Day +1.
Intervention: Melphalan
Lymphodepletion plus Pembrolizumab
Fludarabine \& Melphalan followed by autologous stem cell transplantation. Pembrolizumab will begin on Day +1.
Intervention: Pembrolizumab
Outcomes
Primary Outcomes
Number of Patients With 2-year Relapse Risk
Time Frame: 2 years
Hypothesis is that following lymphodepleting chemotherapy and pembrolizumab, the 2-year relapse risk will decrease to ≤35%
Secondary Outcomes
- Assess Safety of Pembrolizumab by Recording the Number of Participants With Treatment-related Adverse Events(6 months)