Lymphodepletion and Anti-PD-1 Blockade to Reduce Relapse in AML Patient Not Eligible for Transplant

Phase 2

Completed

• Conditions: Acute Myeloid Leukemia
• Interventions: Drug: Fludarabine; Drug: Melphalan; Drug: Pembrolizumab

• Registration Number: NCT02771197
• Lead Sponsor: Northside Hospital, Inc.

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%.

Study Timeline

• Study First Submitted: 2016-03-22
• Study First Submitted QC: 2016-05-10
• Study First Posted: 2016-05-13
• Study Start: 2016-09-28
• Primary Completion: 2022-08-03
• Study Completion: 2023-07-31
• Results First Submitted: 2023-08-25
• Status Verified: 2023-09
• Results First Submitted QC: 2023-09-21
• Results First Posted: 2023-09-22
• Last Update Submitted: 2023-09-22
• Last Update Posted: 2023-09-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Lymphodepletion plus Pembrolizumab	Melphalan	Fludarabine \& Melphalan followed by autologous stem cell transplantation. Pembrolizumab will begin on Day +1.
Lymphodepletion plus Pembrolizumab	Fludarabine	Fludarabine \& Melphalan followed by autologous stem cell transplantation. Pembrolizumab will begin on Day +1.
Lymphodepletion plus Pembrolizumab	Pembrolizumab	Fludarabine \& Melphalan followed by autologous stem cell transplantation. Pembrolizumab will begin on Day +1.

Primary Outcome Measures

Name	Time	Method
Number of Patients With 2-year Relapse Risk	2 years	Hypothesis is that following lymphodepleting chemotherapy and pembrolizumab, the 2-year relapse risk will decrease to ≤35%

Secondary Outcome Measures

Name	Time	Method
Assess Safety of Pembrolizumab by Recording the Number of Participants With Treatment-related Adverse Events	6 months	Assess safety of pembrolizumab in patients with AML following lymphodepleting chemotherapy

Trial Locations

Locations (2)

Northside Hospital; 🇺🇸 Atlanta, Georgia, United States

Blood and Marrow Transplant Group of Georgia; 🇺🇸 Atlanta, Georgia, United States