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

Официальное название

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

Обзор

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.

Вмешательства

• Препарат Donor-Derived Ex-Vivo Expanded Natural Killer Cell Infusions
  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).

Первичные конечные точки

• 1-year RFS [Срок оценки: 1 year]

Вторичные конечные точки (6)

• Number of functional donor-derived NK cells generated from the device [Срок оценки: 2 years]
• GVHD incidence [Срок оценки: 2 years]
• KIR ligand-ligand mismatch [Срок оценки: 2 years]
• Incidence of mixed donor chimerism [Срок оценки: 2 years]
• Cumulative incidence of neutrophil engraftment [Срок оценки: 2 years]
• Cumulative incidence of platelet engraftment [Срок оценки: 2 years]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 13 центров

• Phoenix Children's Hospital — Phoenix
• Children's Hospital Los Angeles — Los Angeles
• Children's Hospital Colorado — Aurora
• AdventHealth Orlando — Orlando
• Johns Hopkins All Children's Hospital — St. Petersburg
• Ann & Robert H. Lurie Children's Hospital — Chicago
• Washington University, St. Louis — St Louis
• New York Medical College — Valhalla
• … и ещё 5 центров

Идентификаторы

NCT: NCT04836390 · CHLA-20-00314

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗