This is a phase II trial designed to test the safety and efficacy (complete response \[CR\]) of related donor HLA-haploidentical NK-cell based therapy for the treatment of acute myelogenous leukemia (AML). Patients with newly diagnosed AML who failed to achieve a complete remission (CR) after one or two standard induction attempts receive after a preparative regimen of cyclophosphamide and fludarabine a single infusion of CD3-/CD19- NK cells or CD3-/CD56+ NK cells followed by a short course of Interleukin-2 (IL-2) to facilitate NK cell survival and expansion.
This trial uses a Simon's two-stage design to estimate the complete remission rate at day +42 post NK cell infusion. The trial includes an initial randomized sub- study of 24 patients during stage 1 to choose which of the enriched NK cell products (CD3-/CD19- versus CD3-/CD56+) should be used to complete the trial based on successful in vivo NK cell expansion. This parameter is defined as 40% donor DNA and 40% of lymphocytes are NK cells at day 7 post infusion OR 20% donor DNA and 20% of lymphocytes are NK cells at day 14 post infusion. Twelve patients will be randomized to each product. Enrollment Plan: Stage 1: Enroll 24 patients with 1:1 randomization for NK cell processing (CD3-/CD19- versus CD3-/CD56+) Stage 2: Enroll an additional 17 patients using the optimal NK cell product identified during stage 1. If neither product achieves success at the end of stage 1, the study will stop and the platform redesigned
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
1
CliniMACS® CD3 and CD19 Reagent System
Universtiy of Chicago
Chicago, Illinois, United States
University of Minnesota
Minneapolis, Minnesota, United States
Ohio State University
Columbus, Ohio, United States
The Primary Endpoint of the Study is Complete Remission (±3 Days)
Both the number of patients with leukemia in complete remission and the number of patients with leukemia not in complete remission will be reported. Leukemia remission status will be assessed according to the Revised Recommendations of The International Working Group (J Clin Oncol 21:4642-4649, 2003).
Time frame: On Day+42 (+/- 3 days) after NK cell infusion
The Secondary Endpoint is the Expansion and Persistence of NK Cells to be Used for the Remainder of the Study.
Successful expansion and persistence of NK cells is defined as ≥ 100 donor derived NK cells per µl blood.
Time frame: Day+7 to Day+42 after NK cell infusion
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