CLINICAL TRIAL article
Front. Immunol.
Sec. Alloimmunity and Transplantation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1601961
This article is part of the Research TopicBalancing Alloantigen-Induced Immune Responses and Anti-tumor Immunity in TransplantationView all 14 articles
Phase I/II clinical trial on the safety and preliminary efficacy of donor-derived anti-leukemia cytotoxic T lymphocytes for the prevention of leukemia relapse in children given haploidentical hematopoietic stem cell transplantation: study rational and design
Provisionally accepted
Daniela Montagna1,2*
Patrizia Comoli1Matteo Tanzi1Enrica Montini1Antonia Moretta1Gloria Taurino1Stella Boghen1Arianna Panigari1Tommaso Mina1Giovanna Giorgiani1Claudia Del Fante1Cesare Perotti1
Marco Zecca1- 1San Matteo Hospital Foundation (IRCCS), Pavia, Lombardy, Italy
- 2University of Pavia, Pavia, Lombardy, Italy
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Leuk-CTL-001 (EudraCT n. 2019-003362-41) is a Phase I/II clinical trial on the safety and preliminary efficacy of donor-derived anti-leukemia cytotoxic T lymphocytes (CTLs) for the prevention of leukemia relapse in children given haploidentical hematopoietic stem cell transplantation (HCT). The prognosis for children affected by acute leukemia and transplanted in an advanced disease stage, in the presence of measurable minimal residual disease (MRD) or with unfavorable cytogenetic abnormalities, is still poor and often less than 50%. Adoptive cell therapy based on the infusion of donor-derived CTLs able to recognize patients' leukemia blasts (LB) is a promising approach to control leukemia relapse after allogeneic HCT. We previously described a procedure for ex vivo generating and expanding large numbers of donor-derived anti-leukemia CTL in compliance with Good Manufacturing Practice (GMP). The analysis of all batches of anti-leukemia CTLs produced so far documented that the majority of effector cells were CD3+/CD8+ cells, with a memory/terminal activated phenotype displaying efficient capacity to lyse patients' LB and to secrete IFN-gamma and TNF-alfa in response to leukemia cells. The Leuk-001 trial explores the safety of infusion of escalating doses of anti-leukemia CTLs in a cohort of high-risk relapse pediatric patients given haploidentical HCT for acute leukemia, starting within 60 days after transplantation. The safety is evaluated in terms of incidence of acute and chronic graft versus host disease (GVHD). The secondary objective is the evaluation of efficacy defined as cumulative incidence of relapse.
Keywords: cytotoxic T lymphocytes, Haploidentical hematopoietic stem cell transplantation, adoptive cell therapy, Pediatric acute leukemia, graft-versus-host-disease
Received: 28 Mar 2025; Accepted: 02 May 2025.
Copyright: © 2025 Montagna, Comoli, Tanzi, Montini, Moretta, Taurino, Boghen, Panigari, Mina, Giorgiani, Fante, Perotti and Zecca. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Daniela Montagna, San Matteo Hospital Foundation (IRCCS), Pavia, 27100, Lombardy, Italy
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