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

September 22, 2023 updated by: Northside Hospital, Inc.

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Georgia
      • Atlanta, Georgia, United States, 30342
        • Blood and Marrow Transplant Group of Georgia
      • Atlanta, Georgia, United States, 30342
        • Northside Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 78 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Lymphodepletion plus Pembrolizumab
Fludarabine & Melphalan followed by autologous stem cell transplantation. Pembrolizumab will begin on Day +1.
Drug: Pembrolizumab
Drug: Fludarabine
Drug: Melphalan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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%
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Northside Hospital, Inc.

Collaborators

Merck Sharp & Dohme LLC

Investigators

  • Principal Investigator: Scott Solomon, MD, Blood and Marrow Transplant Group of Georgia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 28, 2016

Primary Completion (Actual)

August 3, 2022

Study Completion (Actual)

July 31, 2023

Study Registration Dates

First Submitted

March 22, 2016

First Submitted That Met QC Criteria

May 10, 2016

First Posted (Estimated)

May 13, 2016

Study Record Updates

Last Update Posted (Actual)

September 28, 2023

Last Update Submitted That Met QC Criteria

September 22, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NSH 1150

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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