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

NCT04836390 | Enrolling By Invitation Phase 2 DMC FDA Drug

• 1 other identifier: CHLA-20-00314
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 13

Brief Summary

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.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• 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)

  1 year

Secondary Outcomes (6)

• Number of functional donor-derived NK cells generated from the device

  2 years

• GVHD incidence

  2 years

• KIR ligand-ligand mismatch

  2 years

• Incidence of mixed donor chimerism

  2 years

• Cumulative incidence of neutrophil engraftment

  2 years

Study Arms (1)

Treatment Arm

EXPERIMENTAL

All subjects will receive NK infusions.

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

Interventions

Donor-Derived Ex-Vivo Expanded Natural Killer Cell Infusions DRUG

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).

Treatment Arm

Eligibility Criteria

• Age: 0 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Michael Pulsipher: lead
• Nationwide Children's Hospital: collaborator
• Seattle Children's Hospital: collaborator

Study Sites (13)

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

AdventHealth Orlando

Orlando, Florida, 32803, United States

Location

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

Ann & Robert H. Lurie Children's Hospital

Chicago, Illinois, 60611, United States

Location

Washington University, St. Louis

St Louis, Missouri, 63110, United States

Location

New York Medical College

Valhalla, New York, 10595, United States

Location

Cleveland Clinic Lerner College of Medicine

Cleveland, Ohio, 44195, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Fred Hutchinson Cancer Center

Seattle, Washington, 95109, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Michael L Pulsipher, MD

  Children's Hospital Los Angeles

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: March 18, 2021
• First Posted: April 8, 2021
• Study Start: August 24, 2021
• Primary Completion: May 1, 2026
• Study Completion (Estimated): May 1, 2028
• Last Updated: May 4, 2025

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data will be available for an additional 2-3 years.
• Access Criteria: Contact Principal Investigator

Locations

US (13)