Michael Pulsipher
This is a Phase II pilot study to determine the efficacy of three fixed dose (1 x 108/kg) infusions of ex-vivo expanded human leukocyte antigen (HLA)-haploidentical donor natural killer (NK) cells (haploNK) in children and young adults with high risk acute myeloid leukemia (AML) undergoing HLA-haploidentical hematopoietic cell transplant (haploHCT) with a busulfan and cyclophosphamide-based myeloablative conditioning regimen and post-transplant cyclophosphamide (PTCy) for graft versus host disease (GVHD) prophylaxis. The investigators will also demonstrate the feasibility of performing this trial in a multi-center study. The investigators hypothesize that the infusion of haploNK in this setting will facilitate immune reconstitution and decrease relapse rates and infectious complications without increasing GVHD, resulting in improved survival as compared to recent historical cohorts of haploHCT without NK cell infusion.
Inclusion Criteria: * Age ≤ 25 years at time of enrollment * High-risk AML, as defined by one of the following: * AML in CR1 (defined as \<5% blasts in BM by morphology and flow cytometry) having at least one of these high-risk features: * Mutations associated with high risk disease (Appendix A). Other high-risk features not explicitly stated in Appendix A can be considered after discussion/approval with the protocol chair/team * MRD-positive at the end of Induction I chemotherapy (defined as flow cytometry ≥ 0.1% blasts) * AML in ≥CR2 (defined by \<5% blasts in BM by morphology and flow cyto…
Peripheral blood (PB) ≤ 450 mL and based on donor weight (minimum 10 ml/kg) will be drawn from the HLA-haploidentical donor at least 16 days before the scheduled day of transplant (Day 0). HaploNK cells will be manufactured from the PB of the donor after co-culture with irradiated feeder cells (IFC) as described in Section 2.4. The recipients will receive three NK cell infusions on Day-1, Day+7 (± 1 day) and Day+42 (up to Day+90) from day of transplant (Day 0).