Donor-Derived Ex-Vivo Expanded Natural Killer Cell Infusions in Children and Young Adults With High Risk Acute Myeloid Leukemia Receiving Myeloablative HLA-Haploidentical Hematopoietic Cell Transplant
Sponsor: Michael Pulsipher
ClinicalTrials ID:NCT04836390
This Phase II pilot study evaluates the efficacy of three fixed-dose infusions of ex-vivo expanded haploNK cells in children and young adults with high-risk AML undergoing haploHCT. Eligible participants are ≤25 years with specific high-risk AML criteria and adequate organ function. The intervention involves NK cell infusions derived from HLA-haploidentical donors, administered pre- and post-transplant.
Patient Parameters
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Program Overview
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.
Eligibility Criteria
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 cytometry)
- Recovery from prior cycle of chemotherapy as defined by an absolute neutrophil count ≥ 500/mm3
- AML secondary to select germline marrow failure disorders (with exception of Fanconi Anemia) may be eligible but require approval from Protocol Chairs prior to enrollment.
- Performance status ≥70% (Lansky for <16 years; Karnofsky for ≥16 years)
- Adequate major organ system function as demonstrated by:
- Renal: Creatinine clearance (CrCl) ≥60 mL/min/1.73m2 by Cockcroft-Gault formula, Schwartz formula, or nuclear GFR study (Table 3)
- Hepatic: Total bilirubin <2 mg/dL (unless due to Gilbert syndrome) and ALT and AST < 5x ULN
- Cardiac: LVEF at rest ≥50% or SF ≥27% (by MUGA or ECHO)
- Pulmonary: DLCO, FEV1, and FVC ≥ 50% of predicted corrected for hemoglobin. For patients <7 years of age or those unable to perform PFTs: O2 Sat >92% on room air by pulse oximetry and on no supplemental O2 at rest
- The patient, patient's parent, guardian, or legal representative can provide written informed consent
Exclusion Criteria
- Active extramedullary disease
- Unresolved/ongoing and serious viral, bacterial, or fungal infection despite appropriate treatment
- Positive pregnancy test in a female of child-bearing potential (FCBP)
- Inability to comply with medical therapy or follow-up
- Prior allogeneic transplant
- Patients with Fanconi Anemia and Down syndrome
Locations
| FACILITY | ZIP | CITY | STATE |
|---|---|---|---|
| Phoenix Children's Hospital | 85016 | Phoenix | Arizona |
| Children's Hospital Los Angeles | 90027 | Los Angeles | California |
| Children's Hospital Colorado | 80045 | Aurora | Colorado |
| AdventHealth Orlando | 32803 | Orlando | Florida |
| Johns Hopkins All Children's Hospital | 33701 | St. Petersburg | Florida |
| Ann & Robert H. Lurie Children's Hospital | 60611 | Chicago | Illinois |
| Washington University, St. Louis | 63110 | St Louis | Missouri |
| New York Medical College | 10595 | Valhalla | New York |
| Cleveland Clinic Lerner College of Medicine | 44195 | Cleveland | Ohio |
| Nationwide Children's Hospital | 43205 | Columbus | Ohio |
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