Phase 2 Clinical Trial of Infusing Haploidentical K562-mb15-41BBL-Activated and Expanded Natural Killer Cells as Consolidation Therapy for Pediatric Acute Myeloblastic Leukemia.


Journal

Clinical lymphoma, myeloma & leukemia
ISSN: 2152-2669
Titre abrégé: Clin Lymphoma Myeloma Leuk
Pays: United States
ID NLM: 101525386

Informations de publication

Date de publication:
05 2021
Historique:
received: 12 12 2020
revised: 17 01 2021
accepted: 19 01 2021
pubmed: 22 2 2021
medline: 29 1 2022
entrez: 21 2 2021
Statut: ppublish

Résumé

Acute myeloid leukemia (AML) accounts for approximately 20% of pediatric leukemia cases; 30% of these patients experience relapse. The antileukemia properties of natural killer (NK) cells and their safety profile have been reported in AML therapy. We proposed a phase 2, open, prospective, multicenter, nonrandomized clinical trial for the adoptive infusion of haploidentical K562-mb15-41BBL-activated and expanded NK (NKAE) cells as a consolidation strategy for children with favorable and intermediate risk AML in first complete remission after chemotherapy (NCT02763475). Before the NKAE cell infusion, patients underwent a lymphodepleting regimen. After the NKAE cell infusion, patients were administered low doses (1 × 10 Seven patients (median age, 7.4 years; range, 0.78-15.98 years) were administered 13 infusions of NKAE cells, with a median of 36.44 × 10 This study emphasizes the difficulties in recruiting patients for cell therapy trials, though NKAE cell infusion is safe and feasible. However, we cannot draw any conclusions regarding efficacy because of the small number of included patients and insufficient biological markers.

Sections du résumé

BACKGROUND
Acute myeloid leukemia (AML) accounts for approximately 20% of pediatric leukemia cases; 30% of these patients experience relapse. The antileukemia properties of natural killer (NK) cells and their safety profile have been reported in AML therapy. We proposed a phase 2, open, prospective, multicenter, nonrandomized clinical trial for the adoptive infusion of haploidentical K562-mb15-41BBL-activated and expanded NK (NKAE) cells as a consolidation strategy for children with favorable and intermediate risk AML in first complete remission after chemotherapy (NCT02763475).
PATIENTS AND METHODS
Before the NKAE cell infusion, patients underwent a lymphodepleting regimen. After the NKAE cell infusion, patients were administered low doses (1 × 10
RESULTS
Seven patients (median age, 7.4 years; range, 0.78-15.98 years) were administered 13 infusions of NKAE cells, with a median of 36.44 × 10
CONCLUSION
This study emphasizes the difficulties in recruiting patients for cell therapy trials, though NKAE cell infusion is safe and feasible. However, we cannot draw any conclusions regarding efficacy because of the small number of included patients and insufficient biological markers.

Identifiants

pubmed: 33610500
pii: S2152-2650(21)00021-5
doi: 10.1016/j.clml.2021.01.013
pii:
doi:

Banques de données

ClinicalTrials.gov
['NCT02763475']

Types de publication

Clinical Trial, Phase II Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

328-337.e1

Informations de copyright

Copyright © 2021 Elsevier Inc. All rights reserved.

Auteurs

Lara Maria Gómez García (LM)

Hematology Department, University Clinic Hospital of Valladolid, Valladolid, Spain.

Adela Escudero (A)

Institute of Medical and Molecular Genetics (INGEMM), La Paz University Hospital, Madrid, Spain.

Carmen Mestre (C)

Translational Research in Pediatric Oncology, Hematopoietic Transplantation and Cell Therapy, IdiPAZ, Madrid, Spain.

Jose L Fuster Soler (JL)

Pediatric Hematology-Oncology Unit, University Clinic Hospital Virgen de la Arrixaca, El Palmar, Spain.

Antonia Pascual Martínez (AP)

Pediatric Hematology Unit, Maternal and Children Hospital, Regional University Hospital of Málaga, Málaga, Spain.

Jose M Vagace Valero (JM)

Pediatric Hematology Department, Maternal Pediatric Hospital, University Hospital Complex of Badajoz, Badajoz, Spain.

María Vela (M)

Translational Research in Pediatric Oncology, Hematopoietic Transplantation and Cell Therapy, IdiPAZ, Madrid, Spain.

Beatriz Ruz (B)

Institute of Medical and Molecular Genetics (INGEMM), La Paz University Hospital, Madrid, Spain.

Alfonso Navarro (A)

Translational Research in Pediatric Oncology, Hematopoietic Transplantation and Cell Therapy, IdiPAZ, Madrid, Spain.

Lucia Fernández (L)

Hematological Malignancies Clinical Research Unit, National Center for Cancer Research (CNIO), Madrid, Spain.

Adrián Fernández (A)

Hematological Malignancies Clinical Research Unit, National Center for Cancer Research (CNIO), Madrid, Spain.

Alejandra Leivas (A)

Hematological Malignancies Clinical Research Unit, National Center for Cancer Research (CNIO), Madrid, Spain.

Joaquin Martínez-López (J)

Hematological Malignancies Clinical Research Unit, National Center for Cancer Research (CNIO), Madrid, Spain.

Cristina Ferreras (C)

Translational Research in Pediatric Oncology, Hematopoietic Transplantation and Cell Therapy, IdiPAZ, Madrid, Spain.

Raquel De Paz (R)

Hematology Department, La Paz University Hospital, Madrid, Spain.

Miguel Blanquer (M)

Pediatric Hematology-Oncology Unit, University Clinic Hospital Virgen de la Arrixaca, El Palmar, Spain.

Victor Galán (V)

Pediatric Onco-Hematology Department, La Paz University Hospital, Madrid, Spain.

Berta González (B)

Pediatric Onco-Hematology Department, La Paz University Hospital, Madrid, Spain.

Dolores Corral (D)

Pediatric Onco-Hematology Department, La Paz University Hospital, Madrid, Spain.

Luisa Sisinni (L)

Pediatric Onco-Hematology Department, La Paz University Hospital, Madrid, Spain.

Isabel Mirones (I)

Pediatric Onco-Hematology Department, La Paz University Hospital, Madrid, Spain.

Antonio Balas (A)

Histocompatibility and HLA Typing Laboratory, Transfusion Center of the Community of Madrid, Madrid, Spain.

José Luis Vicario (JL)

Histocompatibility and HLA Typing Laboratory, Transfusion Center of the Community of Madrid, Madrid, Spain.

Paula Valle (P)

Clinical Pharmacology Department, La Paz University Hospital, Madrid, Spain.

Alberto M Borobia (AM)

Clinical Pharmacology Department, La Paz University Hospital, Madrid, Spain.

Antonio Pérez-Martínez (A)

Institute of Medical and Molecular Genetics (INGEMM), La Paz University Hospital, Madrid, Spain; Translational Research in Pediatric Oncology, Hematopoietic Transplantation and Cell Therapy, IdiPAZ, Madrid, Spain; Pediatric Onco-Hematology Department, La Paz University Hospital, Madrid, Spain; Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain. Electronic address: aperezmartinez@salud.madrid.org.

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