VEN+DAC+Bu2Flu4 vs Bu2Flu5 Conditioning Regimen for Elderly Myeloid Malignancies Undergoing Allo-HSCT

Официальное название

Venetoclax+Decitabine+Busulfan+Fludarabine (VEN+DAC+Bu2Flu4) vs Busulfan+Fludarabine Conditioning Regimen (Bu2Flu5 ) for Older Patients With Myeloid Malignancies Undergoing Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT)

Обзор

The purpose of this study is to compare the efficacy and safety of venetoclax+decitabine+busulfan+fludarabine (VEN+DAC+Bu2Flu4) regimen with busulfan+fludarabine (Bu2Flu5) regimen in older patients with myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Подробное описание

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potent curative approach for myeloid malignancies, but outcomes post-transplantation of older population were unsatisfactory. The conditioning regimen is an essential factor affecting outcomes post-transplantation. Currently, the optimal conditioning for older patients with myeloid malignancies remains unclear. Myeloablative conditioning (MAC) regimens like busulfan plus cyclophosphamide, and busulfan plus fludarabine (Bu4Flu4-5) have low relapse rates, but high non-relapse mortality (NRM) is observed in older patients with myeloid malignancies. The development of reduced-intensity conditioning (RIC) regimens such as Bu2Flu5 has decreased NRM and enhanced the feasibility of allo-HSCT in older patients with myeloid malignancies, but it appears to have higher relapse rate. Neither conventional MAC nor RIC regimens benefit older patients with myeloid malignancies. In recent years, some studies reported that the introduction of venetoclax (VEN) or decitabine (DAC) to MAC reduced relapse without increasing NRM in younger patients with high-risk myeloid malignancies. However, whether VEN and DAC combined with RIC regimen reduce relapse without increasing NRM, then improve survival in older patients with myeloid malignancies is unclear. Therefore, we conducted a randomized controlled study to compare the efficacy and safety of VEN+DAC+Bu2Flu4 with Bu2Flu5 in older patients with myeloid malignancies undergoing allo-HSCT.

Вмешательства

• Препарат Venetoclax (VEN)
  Venetoclax (VEN) was administered at 400mg/day on days -10 to -4.
• Препарат Decitabine (DAC)
  Decitabine (DAC) was administered at 20mg/m2/day on days -10 to -8.
• Препарат Busulfan (Bu)
  Busulfan (Bu) was administered at 3.2 mg/kg/day on days -5 to -4.
• Препарат Fludarabine (Flu)
  Fludarabine (Flu) was administered at 30mg/m2/day on days -5 to -2.
• Препарат Fludarabine (Flu)
  Fludarabine (Flu) was administered at 30mg/m2/day on days -6 to -2.

Первичные конечные точки

• Disease-free survival (DFS) rate [Срок оценки: 2 year]

Вторичные конечные точки (3)

• Overall survival (OS) rate [Срок оценки: 2 year]
• Relapse incidence [Срок оценки: 2 year]
• Non-relapse mortality (NRM) incidence [Срок оценки: 2 year]

Критерии участия

Критерии включения

• 60-75 years
• Acute myeloid leukaemia in first complete remission or myelodysplastic syndrome
• Willing to undergo the first allo-HSCT
• Eastern Cooperative Oncology Group performance status of 0-2

Критерии исключения

• Any abnormality in a vital sign (e.g., heart rate, respiratory rate, or blood pressure)
• Patients with any conditions not suitable for the trial (investigators' decision)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Ling Y, Xuan L, Xu N, Huang F, Fan Z, Guo Z, Xu X, Liu H, Lin R, Yu S, Zhang H, Jin H, Wu M, Liu C, Liang X, Ou R, Zhang Y, Liu X, Qu H, Zhai X, Sun J, Zhao Y, Liu Q. Busulfan Plus Fludarabine Compared With Busulfan Plus Cyclophosphamide for AML Undergoing HLA-Haploidentical Hematopoietic Cell Transplantation: A Multicenter Randomized Phase III Trial. J Clin Oncol. 2023 Oct 10;41(29):4632-4642. do PMID 37335960
• Rambaldi A, Grassi A, Masciulli A, Boschini C, Mico MC, Busca A, Bruno B, Cavattoni I, Santarone S, Raimondi R, Montanari M, Milone G, Chiusolo P, Pastore D, Guidi S, Patriarca F, Risitano AM, Saporiti G, Pini M, Terruzzi E, Arcese W, Marotta G, Carella AM, Nagler A, Russo D, Corradini P, Alessandrino EP, Torelli GF, Scime R, Mordini N, Oldani E, Marfisi RM, Bacigalupo A, Bosi A. Busulfan plus cyc PMID 26429297
• Devine SM, Owzar K, Blum W, Mulkey F, Stone RM, Hsu JW, Champlin RE, Chen YB, Vij R, Slack J, Soiffer RJ, Larson RA, Shea TC, Hars V, Sibley AB, Giralt S, Carter S, Horowitz MM, Linker C, Alyea EP. Phase II Study of Allogeneic Transplantation for Older Patients With Acute Myeloid Leukemia in First Complete Remission Using a Reduced-Intensity Conditioning Regimen: Results From Cancer and Leukemia G PMID 26527780
• Xuan L, Dai M, Jiang E, Wang Y, Huang F, Fan Z, Xu N, Nie D, Liang X, Chen H, Ye J, Shi P, Liu H, Jin H, Lin R, Yan C, Zhang Y, Sun J, Han M, Liu Q. The effect of granulocyte-colony stimulating factor, decitabine, and busulfan-cyclophosphamide versus busulfan-cyclophosphamide conditioning on relapse in patients with myelodysplastic syndrome or secondary acute myeloid leukaemia evolving from myelod PMID 36702138
• Zheng X, Gao H, Lu N, Wang M, Zhang H, Zheng Y, Shen B, Cao Y, Chen X, Zhai W, Wei J, Yang D, Zhang R, Pang A, Feng S, Jiang E, Han M. Efficacy of venetoclax combined with decitabine conditioning regimen for allogeneic hematopoietic stem cell transplantation in high-risk and elderly patients with myeloid neoplasms. Ann Hematol. 2023 Dec;102(12):3603-3611. doi: 10.1007/s00277-023-05500-2. Epub 2023 PMID 37878011

Идентификаторы

NCT: NCT07052422 · NFEC-2025-260

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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