Early Use of Tacrolimus in HLA-Mismatched Haploidentical Allogeneic Hematopoietic Transplantation With Post-Transplant Cyclophosphamide

Обзор

To evalute the safety and efficacy in reducing Cytokine Release Syndrome after hematopoietic stem cell transplantation by introducing immunosuppression earlier in the transplant process

Вмешательства

• Препарат Tacrolimus
  Begins Day -1 and continues to Day +90 or Day +180 after transplant
• Препарат Cyclophosphamide
  Given Days +3 and +4 after transplant
• Препарат Mycofenolate mofetil
  Given Day 0 to Day +35 after transplant

Первичные конечные точки

• Efficacy in preventing CRS post transplant [Срок оценки: 30 days]

Вторичные конечные точки (3)

• Severity of CRS after stem cell transplant [Срок оценки: 30 days]
• Safety of administering early immunosuppression [Срок оценки: 6 months]
• Safety of administering early immunosuppression [Срок оценки: 1 year]

Критерии участия

Критерии включения

• Availability of a 5/10-8/10 mismatched (HLA-A, B, DR) haploidentical related donor with a negative HLA cross-match in the host vs. graft direction and willing to provide peripheral blood stem cells
• Karnofsky status >/= 70%
• Hematologic malignancy requiring allogeneic transplantation
• First allogeneic transplant only. Prior autologous transplant is allowed.

Критерии исключения

• Poor cardiac function: LVEF <40%
• Poor pulmonary function: FEV1 and FVC <50% predicted
• Poor liver function: bilirubin >/= 3mg/dL (not due to hemolysis, Gilbert's or primary malignancy)
• Poor renal function: Creatinine >/= 2mg/dL or creatinine clearance (calculated or measured creatinine clearance is permitted) <40mL/min based on Traditional Cockcroft-Gault formula
• Women of childbearing potential who currently are pregnant or who are not practicing adequate contraception
• Patients who have any debilitating medical or psychiatric illness that would preclude their giving informed consent or their receiving optimal treatment and follow up

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 · 1 центр

• Northside Hospital — Atlanta

Публикации

• Solh MM, Dickhaus E, Solomon SR, Morris LE, Zhang X, Holland HK, Bashey A. Fevers post infusion of T-cell replete hla mismatched haploidentical hematopoietic stem cells with post-transplant cyclophosphamide: risk factors and impact on transplant outcomes. Bone Marrow Transplant. 2019 Nov;54(11):1756-1763. doi: 10.1038/s41409-019-0522-4. Epub 2019 Apr 5. PMID 30953027
• Tang J, Jensen RR, Bryan B, Hoda D, Hunter BD. Reduced Cytokine Release Syndrome and Improved Outcomes with Earlier Immunosuppressive Therapy in Haploidentical Stem Cell Transplantation. Transplant Cell Ther. 2024 Apr;30(4):438.e1-438.e11. doi: 10.1016/j.jtct.2024.01.076. Epub 2024 Jan 26. PMID 38281591
• Abboud R, Wan F, Mariotti J, Arango M, Castagna L, Romee R, Hamadani M, Chhabra S. Cytokine release syndrome after haploidentical hematopoietic cell transplantation: an international multicenter analysis. Bone Marrow Transplant. 2021 Nov;56(11):2763-2770. doi: 10.1038/s41409-021-01403-w. Epub 2021 Jul 14. PMID 34262142
• Abboud R, Keller J, Slade M, DiPersio JF, Westervelt P, Rettig MP, Meier S, Fehniger TA, Abboud CN, Uy GL, Vij R, Trinkaus KM, Schroeder MA, Romee R. Severe Cytokine-Release Syndrome after T Cell-Replete Peripheral Blood Haploidentical Donor Transplantation Is Associated with Poor Survival and Anti-IL-6 Therapy Is Safe and Well Tolerated. Biol Blood Marrow Transplant. 2016 Oct;22(10):1851-1860. do PMID 27318038
• Ruggeri A, Labopin M, Battipaglia G, Chiusolo P, Tischer J, Diez-Martin JL, Bruno B, Castagna L, Moiseev IS, Vitek A, Rovira M, Ciceri F, Bacigalupo A, Nagler A, Mohty M. Timing of Post-Transplantation Cyclophosphamide Administration in Haploidentical Transplantation: A Comparative Study on Behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Bio PMID 32645444
• Chiusolo P, Bug G, Olivieri A, Brune M, Mordini N, Alessandrino PE, Dominietto A, Raiola AM, Di Grazia C, Gualandi F, Van Lint MT, Ferrara F, Finizio O, Angelucci E, Bacigalupo A. A Modified Post-Transplant Cyclophosphamide Regimen, for Unmanipulated Haploidentical Marrow Transplantation, in Acute Myeloid Leukemia: A Multicenter Study. Biol Blood Marrow Transplant. 2018 Jun;24(6):1243-1249. doi: 1 PMID 29421292
• Bashey A, Zhang X, Sizemore CA, Manion K, Brown S, Holland HK, Morris LE, Solomon SR. T-cell-replete HLA-haploidentical hematopoietic transplantation for hematologic malignancies using post-transplantation cyclophosphamide results in outcomes equivalent to those of contemporaneous HLA-matched related and unrelated donor transplantation. J Clin Oncol. 2013 Apr 1;31(10):1310-6. doi: 10.1200/JCO.2012 PMID 23423745
• Mayumi H, Umesue M, Nomoto K. Cyclophosphamide-induced immunological tolerance: an overview. Immunobiology. 1996 Jul;195(2):129-39. doi: 10.1016/S0171-2985(96)80033-7. PMID 8877390

Идентификаторы

NCT: NCT06828796 · NSH 1420

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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