Washington University School of Medicine
This trial represents a single institution phase I/II pilot study with the primary objective of establishing the safety and feasibility of generating and infusing ML NK cells after TCRαβ haplo-HCT.
Patient Inclusion Criteria - Cohort 1: 1. High risk acute myeloid leukemia (AML) in either: 1. Complete remission (CR) defined by \< 5% marrow blasts by morphology in the context of hematological recovery (ANC ≥ 0.5× 10\^9/L, platelet count ≥ 50 × 10\^9/L). 2. Morphological leukemia free state (MLFS) defined by the absence of hematological recovery and \< 5% marrow blasts by morphology 2. Patients must further meet one of the below for inclusion into the study: 1. De novo AML in CR1 with any of the following high-risk features: * MRD ≥ 1% after first induction course *…
rATG is administered intravenously over 6-18 hours for a total of 2 to 3 doses. The daily dose is based on body weight and lymphocyte count.
Busulfan is administered intravenously either Q6H or Q24H, with a recommended target Busulfan AUC of 70-90 mg\*h/L.
Fludarabine is administered intravenously at a dose of 40 mg/m\^2/dose once daily for 4 days.
Thiotepa is administered intravenously at a dose of 5 mg/kg/dose Q12H for 2 doses.
Melphalan is administered intravenously at a dose of 70 mg/m\^2/dose once daily for 2 days.
The HPC product obtained from a haploidentical donor will undergo ex vivo TCR alpha beta and CD19+ depletion, and will be infused fresh on Day 0. There is no maximum limit for CD34+ dose. A maximum dose of 1 x 10\^5/kg recipient weight of TCRαβ cells should not be exceeded in the final HPC product.
The ML NK cells (dose: max capped at 20 x 10\^6/kg recipient weight, minimum dose allowed is 0.5 x 10\^6/kg recipient weight) will be infused on Day +7.
IL-2 is administered subcutaneously at a dose of 1 million units/m\^2 on Days +7, +9, +11, +13, +15, +17, and +19 (7 doses total).
If suboptimal collection of stem cells is predicted, plerixafor may be administered at a dose of 0.24 mg/kg subcutaneous injection once (maximum 40mg/dose). For patients with renal impairment, plerixafor will be administered at a dose of 0.16 mg/kg subcutaneous injection (maximum 27 mg/day).
G-CSF will be administered at a dose of 10 mcg/kg/day for 5 days, or 6 days if two days of collection are needed.
After stem cells are collected by leukapheresis, in order to create the HPC product, the stem cells will be washed to remove platelets and the cell concentration will be adjusted per laboratory and CliniMACS technology recommendations. The cells are then labeled using the CliniMACS TCRαβ Biotin Kit and CD19+ immunomagnetic microbeads. After labeling, the cells are washed to remove unbound microbeads. The partially processed product is loaded on the CliniMACS device where labeled cells are depleted and the negative fraction is eluted off the device. The negative fraction is centrifuged and volume reconstituted to obtain the final product.
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