Matched Sibling Allogenic Stem Cell Transplantation With Adoptive Immunotherapy With Regulatory And Conventional T Cells For High Risk Acute Myeloid Leukemia

Официальное название

MATCH-Treg: Matched Sibling Allogenic Stem Cell Transplantation With Adoptive Immunotherapy With Regulatory And Conventional T Cells For High Risk Acute Myeloid Leukemia

Обзор

The study is a multicentric, interventional study that evaluates the efficacy of allogeneic HLA-matched allo-HSCT consisting of myeloablative conditioning coupled with donor Treg/Tcon adoptive immunotherapy for high-risk AML patients.

Вмешательства

• Биопрепарат HSCT with Treg/Tcon adoptive immunotherapy
  Purified CD34+ hematopoietic progenitor cells with Treg/Tcon adoptive immunotherapy in allogeneic cell transplantation from HLA-matched related donor

Первичные конечные точки

• Number of participants free from disease 2 years after HSCT [Срок оценки: 2 years]

Вторичные конечные точки (7)

• Number of participants that have reached engraftment 45 days after HSCT [Срок оценки: 45 days]
• Number of participants that developed grade ≥ 2 acute GvHD [Срок оценки: 100 days]
• Number of participants free from chronic GvHD 2 years after HSCT [Срок оценки: 2 years]
• Number of participants who died for transplant related mortality after HSCT [Срок оценки: 2 years]
• Number of patients free from ≥ 2 acute GvHD and/or moderate/severe chronic GvHD and/or relapse [Срок оценки: 2 years]
• Number of patients free from moderate/severe chronic GvHD and relapse [Срок оценки: 2 years]
• Number of patients alive after 2 years after allogeneic transplant [Срок оценки: 2 years]

Критерии участия

Критерии включения

• Diagnosis of AML with adverse genetic mutations in Complete Remission (CR) or incomplete (i) CR according to ELN 2022 recommendations with or without MRD positivity at the time of the HSCT procedure;
• Diagnosis of AML with intermediate genetic mutations in Complete remission (CR) or incomplete (i) CR according to ELN 2022 with MRD positivity at the time of the transplant;
• Fitness to undergo allo-HCT with myeloablative conditioning regimens according to center policy;
• Availability of a family HLA-matched hematopoietic stem cell donor suitable to be treated with G-CSF (10 mcg/kg/die) for a maximum of 7 days and able to tolerate 2 or more leukaphereses.
• Age ≥ 18 and ≤ 70 years
• ECOG ≤ 2
• HCT-CI ≤ 4
• Signature of the informed consent

Критерии исключения

• Prior allo-HSCT
• AML with favorable genetic abnormalities
• AML with intermediate genetic risk with MRD negativity
• Active disease at transplant (> 5% bone marrow infiltration)
• Availability of a haploidentical or matched unrelated donor (MUD)
• Age < 18 years or > 70 years
• ECOG > 2
• Unacceptable lung, liver, kidney, and/or heart function and presence of relevant psychiatric diseases according to clinical judgment
• Uncontrolled bacterial, viral, or fungal infections at time of enrollment
• Pregnancy
• No signature of the informed consent

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

Италия · 2 центра

• Azienda Ospedaliera di Perugia - Ospedale S. Maria della Misericordia — Perugia
• Presidio Ospedaliero Pescara - Azienda Sanitaria Locale di Pescara — Pescara

Публикации

• Pierini A, Ruggeri L, Carotti A, Falzetti F, Saldi S, Terenzi A, Zucchetti C, Ingrosso G, Zei T, Iacucci Ostini R, Piccinelli S, Bonato S, Tricarico S, Mancusi A, Ciardelli S, Limongello R, Merluzzi M, Di Ianni M, Tognellini R, Minelli O, Mecucci C, Martelli MP, Falini B, Martelli MF, Aristei C, Velardi A. Haploidentical age-adapted myeloablative transplant and regulatory and effector T cells for PMID 33646302
• Martelli MF, Di Ianni M, Ruggeri L, Falzetti F, Carotti A, Terenzi A, Pierini A, Massei MS, Amico L, Urbani E, Del Papa B, Zei T, Iacucci Ostini R, Cecchini D, Tognellini R, Reisner Y, Aversa F, Falini B, Velardi A. HLA-haploidentical transplantation with regulatory and conventional T-cell adoptive immunotherapy prevents acute leukemia relapse. Blood. 2014 Jul 24;124(4):638-44. doi: 10.1182/blood- PMID 24923299
• Di Ianni M, Falzetti F, Carotti A, Terenzi A, Castellino F, Bonifacio E, Del Papa B, Zei T, Ostini RI, Cecchini D, Aloisi T, Perruccio K, Ruggeri L, Balucani C, Pierini A, Sportoletti P, Aristei C, Falini B, Reisner Y, Velardi A, Aversa F, Martelli MF. Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation. Blood. 2011 Apr 7;117(14):3921-8. doi: 10.1182/blood-20 PMID 21292771
• Nguyen VH, Zeiser R, Dasilva DL, Chang DS, Beilhack A, Contag CH, Negrin RS. In vivo dynamics of regulatory T-cell trafficking and survival predict effective strategies to control graft-versus-host disease following allogeneic transplantation. Blood. 2007 Mar 15;109(6):2649-56. doi: 10.1182/blood-2006-08-044529. Epub 2006 Nov 9. PMID 17095616

Идентификаторы

NCT: NCT07552649 · MATCH-Treg

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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