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

Northside Hospital, Inc.20 enrolled

Overview

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.

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

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Acute Myeloid Leukemia

Eligibility

Sex: ALLMin age: 18 YearsMax age: 78 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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%

Time frame: 2 years

Secondary Outcomes

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

Time frame: 6 months