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

Northside Hospital, Inc.

Status and phase: Completed; Phase 2

Conditions: Acute Myeloid Leukemia

Treatments: Drug: Melphalan; Drug: Fludarabine; Drug: Pembrolizumab

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02771197

NSH 1150

Details and patient eligibility

About

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 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%.

Enrollment: 20 patients

Sex: All

Ages: 18 to 78 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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20 participants in 1 patient group

Lymphodepletion plus Pembrolizumab

Experimental group

Description:

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

Treatment:

Drug: Melphalan

Drug: Fludarabine

Drug: Pembrolizumab