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 (EXCEL)

Michael Pulsipher

Status and phase

Invitation-only

Phase 2

Conditions

Acute Myeloid Leukemia

Treatments

Drug: Donor-Derived Ex-Vivo Expanded Natural Killer Cell Infusions

Study type

Interventional

Funder types

Other

Identifiers

NCT04836390

CHLA-20-00314

Details and patient eligibility

About

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.

Enrollment

30 estimated patients

Sex

All

Ages

Under 25 years old

Volunteers

No Healthy Volunteers

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