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

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: August 3, 2022

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%.

Interventions

  • Drug: Fludarabine
  • Drug: Melphalan
  • Drug: Pembrolizumab

Arms, Groups and Cohorts

  • Experimental: Lymphodepletion plus Pembrolizumab
    • Fludarabine & Melphalan followed by autologous stem cell transplantation. Pembrolizumab will begin on Day +1.

Clinical Trial Outcome Measures

Primary Measures

  • 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 Measures

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

Participating in This Clinical Trial

Inclusion Criteria

  • Non-favorable risk AML – In CR-1 or subsequent CR – Completed at least one cycle of consolidation chemotherapy – Collection of at least 2×106/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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 78 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Northside Hospital, Inc.
  • Collaborator
    • Merck Sharp & Dohme LLC
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Scott Solomon, MD, Principal Investigator, Blood and Marrow Transplant Group of Georgia

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