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

NCT ID: NCT02771197

Last Updated: 2023-09-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-28
• Study Completion Date: 2023-07-31

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%.

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Lymphodepletion plus Pembrolizumab

Fludarabine \& Melphalan followed by autologous stem cell transplantation. Pembrolizumab will begin on Day +1.

Group Type: EXPERIMENTAL

Fludarabine

Intervention Type: DRUG

Melphalan

Intervention Type: DRUG

Pembrolizumab

Intervention Type: DRUG

Interventions

Fludarabine

Intervention Type: DRUG

Melphalan

Intervention Type: DRUG

Pembrolizumab

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 78 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Northside Hospital, Inc.

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Scott Solomon, MD

Role: PRINCIPAL_INVESTIGATOR

Blood and Marrow Transplant Group of Georgia

Locations

Blood and Marrow Transplant Group of Georgia

Atlanta, Georgia, United States

Northside Hospital

Atlanta, Georgia, United States

Countries

United States

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Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NSH 1150

Identifier Type: -

Identifier Source: org_study_id