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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
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).
Phoenix Children's Hospital
Phoenix, Arizona, United States
Children's Hospital Los Angeles
Los Angeles, California, United States
Children's Hospital Colorado
Aurora, Colorado, United States
AdventHealth Orlando
Orlando, Florida, United States
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, United States
Ann & Robert H. Lurie Children's Hospital
Chicago, Illinois, United States
Washington University, St. Louis
St Louis, Missouri, United States
New York Medical College
Valhalla, New York, United States
Cleveland Clinic Lerner College of Medicine
Cleveland, Ohio, United States
Nationwide Children's Hospital
Columbus, Ohio, United States
...and 3 more locations
1-year RFS
The proportion and corresponding 95% exact binomial CI of patients who are relapse-free at 1-year from day of transplant (Day 0)
Time frame: 1 year
Number of functional donor-derived NK cells generated from the device
Product manufacturing failure is defined as inability to generate sufficient NK cell product due to failure to meet release criteria or insufficient cells for at least one full dose (≤10\^8/NK cells/kg ABW).
Time frame: 2 years
GVHD incidence
The incidence of Grade II- IV aGVHD (Day +100) and cGVHD (Day+180, +1 year), opportunistic infections (+1 year), and OS (+1 year and +2 year).
Time frame: 2 years
KIR ligand-ligand mismatch
The presence of KIR ligand-ligand mismatch between HLA-haploidentical donor and host and the impact on relapse rate.
Time frame: 2 years
Incidence of mixed donor chimerism
Mixed donor chimerism is defined as \>5%, but \<95%, donor cells detected. Full donor chimerism is defined as \>95% donor.
Time frame: 2 years
Cumulative incidence of neutrophil engraftment
The cumulative incidence of neutrophil engraftment from the time of transplant will be estimated using the cumulative incidence function with death and relapse prior to engraftment as the competing risk. The definition of neutrophil engraftment is a post-nadir ANC \> 500/mm3 for three consecutive laboratory values obtained on different days. The first of the three days will be designated as the day of neutrophil recovery.
Time frame: 2 years
Cumulative incidence of platelet engraftment
The cumulative incidence of platelet engraftment from the time of transplant will be estimated using the cumulative incidence function with death and relapse prior to engraftment as the competing risk. The definition of platelet engraftment is sustained platelet count \> 20,000/mm3 with no platelet transfusions in the preceding seven days. The first of three consecutive measurements on different days will be designated as the day of initial platelet recovery.
Time frame: 2 years
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