Description:
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.
Title
- Brief Title: Lymphodepletion and Anti-PD-1 Blockade to Reduce Relapse in AML Patient Not Eligible for Transplant
- Official Title: 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
Clinical Trial IDs
- ORG STUDY ID:
NSH 1150
- NCT ID:
NCT02771197
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Fludarabine | | Lymphodepletion plus Pembrolizumab |
Melphalan | | Lymphodepletion plus Pembrolizumab |
Pembrolizumab | | Lymphodepletion plus Pembrolizumab |
Purpose
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%.
Trial Arms
Name | Type | Description | Interventions |
---|
Lymphodepletion plus Pembrolizumab | Experimental | Fludarabine & Melphalan followed by autologous stem cell transplantation. Pembrolizumab will begin on Day +1. | - Fludarabine
- Melphalan
- Pembrolizumab
|
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
Maximum Eligible Age: | 78 Years |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Estimate the 2-year relapse risk by collecting bone marrow biopsies at the following monthly time points after transplant: 1, 2, 3, 6, 12, 18, and 24 months |
Time Frame: | 2 years |
Safety Issue: | |
Description: | Hypothesis is that following lymphodepleting chemotherapy and pembrolizumab, the 2-year relapse risk will decrease to ≤35% |
Secondary Outcome Measures
Measure: | Assess safety of pembrolizumab by recording the number of participants with treatment-related adverse events |
Time Frame: | 2 years |
Safety Issue: | |
Description: | Assess safety of pembrolizumab in patients with AML following lymphodepleting chemotherapy |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Northside Hospital, Inc. |
Trial Keywords
Last Updated
February 21, 2021