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

Study Overview
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Brief Summary
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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
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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%.

Official Title
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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

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: Fludarabine
* Drug: Melphalan
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 78 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With 2-year Relapse Risk | 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 | Assess safety of pembrolizumab in patients with AML following lymphodepleting chemotherapy | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML