Clinical Trials /

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

NCT02771197

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.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

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

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
FludarabineLymphodepletion plus Pembrolizumab
MelphalanLymphodepletion plus Pembrolizumab
PembrolizumabLymphodepletion 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

NameTypeDescriptionInterventions
Lymphodepletion plus PembrolizumabExperimentalFludarabine & 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

  • AML

Last Updated

November 13, 2019