Safely Delivered Targeted High-dose Irradiation Followed by Adoptive Immunotherapy with Regulatory and Conventional T Cells to Increase Potency of Hematopoietic Stem Cell Transplantation in High-risk Acute Leukemia

Официальное название

SHARP - Safely Delivered Targeted High-dose Irradiation Followed by Adoptive Immunotherapy with Regulatory and Conventional T Cells to Increase Potency of Hematopoietic Stem Cell Transplantation in High-risk Acute Leukemia

Обзор

The study is a monocentric, interventional study that evaluates the efficacy of allogeneic HLA-matched or haploidentical transplantation consisting of an irradiation-based conditioning regimen coupled with donor Treg/Tcon adoptive immunotherapy for high-risk acute leukemia patients.

Вмешательства

• Лучевая терапия total marrow/lymphoid irradiation
  Combination of 20 Gy TMLI with Treg/Tcon adoptive immunotherapy in allogeneic cell transplantation

Первичные конечные точки

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

Вторичные конечные точки (3)

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

Критерии участия

Критерии включения

• AML patients

• Diagnosis of AML with indication to allogeneic hematopoietic cell transplantation.
• Diagnosis of adverse genetic risk leukemia or presence of MRD or active disease (bone marrow infiltration 5-30%) at the time of the transplant procedure.
• Availability of a hematopoietic stem cell donor (family or unrelated HLA-matched or HLA-haploidentical with the patient) 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 ≤ 65 years
• ECOG ≤ 2
• HCT-CI ≤ 4 (51,52)
• Absence of relevant psychiatric diseases
• Signature of the informed consent

ALL patients

• Diagnosis of ALL, either T or B (Philadelphia negative) or mixed phenotype with indication to allogeneic transplant
• Presence of MRD or active disease (bone marrow infiltration 5-30%) or patient with ≥ 2nd complete hematologic remission at the time of the transplant procedure.
• Availability of a hematopoietic stem cell family donor (family or unrelated HLA-matched or HLA-haploidentical with the patient) 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 ≤ 65 years
• ECOG ≤ 2
• HCT-CI ≤ 4
• Absence of relevant psychiatric diseases
• Signature of the informed consent

Критерии исключения

• AML patients

• AML in CR MRD-
• AML with > 5% peripheral blasts or bone marrow infiltration ≥ 30%
• Age < 18 years or > 65 years
• ECOG > 2
• Unacceptable lung, liver, kidney, and/or heart function and presence of relevant psychiatric diseases according to clinical judgment
• Pregnancy
• No signature of the informed consent
• ALL patients

• ALL with > 5% peripheral blasts or bone marrow infiltration ≥30%
• Philadelphia positive ALL
• Age < 18 years or > 65 years
• ECOG > 2
• Unacceptable lung, liver, kidney, and/or heart function and presence of relevant psychiatric diseases according to clinical judgment
• 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 · 1 центр

• Università degli Studi di Perugia — Perugia

Публикации

• Cordonnier C, Einarsdottir S, Cesaro S, Di Blasi R, Mikulska M, Rieger C, de Lavallade H, Gallo G, Lehrnbecher T, Engelhard D, Ljungman P; European Conference on Infections in Leukaemia group. Vaccination of haemopoietic stem cell transplant recipients: guidelines of the 2017 European Conference on Infections in Leukaemia (ECIL 7). Lancet Infect Dis. 2019 Jun;19(6):e200-e212. doi: 10.1016/S1473-30 PMID 30744963
• El Fakih R, Hashmi SK, Ciurea SO, Luznik L, Gale RP, Aljurf M. Post-transplant cyclophosphamide use in matched HLA donors: a review of literature and future application. Bone Marrow Transplant. 2020 Jan;55(1):40-47. doi: 10.1038/s41409-019-0547-8. Epub 2019 May 14. PMID 31089284
• Patil S, Potter V, Mohty M. Review of conditioning regimens for haplo-identical donor transplants using post-transplant cyclophosphamide in recipients of G-CSF mobilised peripheral stem cell. Cancer Treat Rev. 2020 Sep;89:102071. doi: 10.1016/j.ctrv.2020.102071. Epub 2020 Jul 15. PMID 32717620
• Chistolini P, Cossu G, De Luca M, Marazzi M, Mavilio F, Migliaccio G, et al. LINEE GUIDA PER L'INGEGNERIA DEI TESSUTI E LA TERAPIA CELLULARE. Not DellIstituto Super Sanità. 1999 May 1;Vol. 12:1-8
• Stern M, Ruggeri L, Mancusi A, Bernardo ME, de Angelis C, Bucher C, Locatelli F, Aversa F, Velardi A. Survival after T cell-depleted haploidentical stem cell transplantation is improved using the mother as donor. Blood. 2008 Oct 1;112(7):2990-5. doi: 10.1182/blood-2008-01-135285. Epub 2008 May 20. PMID 18492955
• Ruggeri L, Capanni M, Urbani E, Perruccio K, Shlomchik WD, Tosti A, Posati S, Rogaia D, Frassoni F, Aversa F, Martelli MF, Velardi A. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science. 2002 Mar 15;295(5562):2097-100. doi: 10.1126/science.1068440. PMID 11896281
• Ciurea SO, Cao K, Fernandez-Vina M, Kongtim P, Malki MA, Fuchs E, Luznik L, Huang XJ, Ciceri F, Locatelli F, Aversa F, Castagna L, Bacigalupo A, Martelli M, Blaise D, Handgretinger R, Roy DC, O'Donnell P, Bashey A, Lazarus HM, Ballen K, Savani BN, Mohty M, Nagler A. The European Society for Blood and Marrow Transplantation (EBMT) Consensus Guidelines for the Detection and Treatment of Donor-specif PMID 29335625
• van der Velden VH, Panzer-Grumayer ER, Cazzaniga G, Flohr T, Sutton R, Schrauder A, Basso G, Schrappe M, Wijkhuijs JM, Konrad M, Bartram CR, Masera G, Biondi A, van Dongen JJ. Optimization of PCR-based minimal residual disease diagnostics for childhood acute lymphoblastic leukemia in a multi-center setting. Leukemia. 2007 Apr;21(4):706-13. doi: 10.1038/sj.leu.2404535. Epub 2007 Feb 8. PMID 17287857

Идентификаторы

NCT: NCT06845592 · SHARP

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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