Clinical trial NCT04836390: 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
Official title: A Phase II Pilot Study of 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: A Multicenter Pediatric Transplantation and Cellular Therapy Consortium (PTCTC) Study
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Lead sponsor: Pediatric Transplantation & Cellular Therapy Consortium
Sponsor class: OTHER
Collaborators: name: Nationwide Children's Hospital
name: Seattle Children's Hospital
First posted: 2021-04-08
Enrollment: 30
Sex: ALL
Minimum age (years): 0
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: 1-year RFS
timeFrame: 1 year
Secondary outcomes:
measure: Number of functional donor-derived NK cells generated from the device
timeFrame: 2 years
measure: GVHD incidence
timeFrame: 2 years
measure: KIR ligand-ligand mismatch
timeFrame: 2 years
measure: Incidence of mixed donor chimerism
timeFrame: 2 years
measure: Cumulative incidence of neutrophil engraftment
timeFrame: 2 years
measure: Cumulative incidence of platelet engraftment
timeFrame: 2 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Orlando
country: United States
facility: AdventHealth Orlando
state: Florida
city: St. Petersburg
country: United States
facility: Johns Hopkins All Children's Hospital
state: Florida
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital
state: Illinois
city: St. Louis
country: United States
facility: Washington University, St. Louis
state: Missouri
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Lerner College of Medicine
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Children's Hospital Los Angeles
name: Michael L Pulsipher, MD
role: STUDY_DIRECTOR
References: