Conditioning Regimen in Elderly AML Patients Receiving Haplo-HSCT.

Официальное название

Bu/Cy/Flu/ATG Versus Bu/Cy/ATG Conditioning Regimen in Elderly AML Patients Receiving Haploidentical Hematopoietic Stem Cell Transplantation: a Prospective, Randomized, Controlled Study

Обзор

Elderly AML patients receiving conventional chemotherapy have poor prognosis. Allo-HSCT offers better long-term survival than chemotherapy, while high TRM limits its use. Current research focuses more on improving conditioning regimens to reduce TRM. Studies suggest Bu/Flu/Cy/ATG are safer and more effective for elderly AML haplo-HSCT, lowering TRM. However, prospective randomized trials are lacking. This study aims to compare Bu/Flu/Cy/ATG vs. Bu/Cy/ATG to determine if TRM can be reduced in elderly AML undergoing haplo-HSCT.

Подробное описание

The prognosis of elderly patients with acute myeloid leukemia (AML) undergoing conventional chemotherapy is poor. Compared with chemotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) can improve long-term survival in elderly patients. However, the high transplantion-related mortality (TRM) limited its application. Currently, the top priority in transplantation for elderly AML patients is to reduce TRM through methods such as optimizing conditioning regimens, reducing graft-versus-host disease (GVHD), and preventing infections. Present research primarily focuses on optimizing conditioning regimens. Both domestic and international studies, as well as our team's preliminary research, suggest that replacing cyclophosphamide (Cy) with fludarabine (Flu) can reduce toxicity. Earlier prospective single-arm clinical study in our team confirmed that the Bu/Flu/Cy/ATG regimen is a safe and effective conditioning protocol for haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in elderly AML patients. This study aims to use a prospective randomized controlled trial to verify whether the Bu/Flu/Cy/ATG conditioning regimen can reduce TRM compared with the Bu/Cy/ATG regimen in elderly AML patients undergoing haplo-HSCT.

Вмешательства

• Процедура Bu/Flu/Cy/ATG
  The Bu/Flu/Cy/ATG conditioning regimen consists of the following components: Ara-C (2 g/m²/day, injected i.v.) on days-10 and-9; Bu (0.8 mg/kg, q6h, injected i.v.) on days -8 to -6; Flu (30 mg/m²/day, injected i.v.) from day-6 to day-2; Cy (1.0 g/m²/day, injected i.v.) on days-5 and-4; and ATG (2.5 mg/kg/day) on days-5 to -2.
• Процедура Bu/Cy/ATG
  The Bu/Cy/ATG conditioning regimen consists of the following components: Ara-C (4 g/m²/day, injected i.v.) on day-9; Bu (0.8 mg/kg, q6h, injected i.v.) on days -8 to -6; Cy (1.8 g/m²/day, injected i.v.) on days-5 and-4; and ATG (2.5 mg/kg/day) on days-5 to -2.

Первичные конечные точки

• Transplant-related mortality (TRM) [Срок оценки: From HSCT to the follow-up assessment at 12 months post-treatment.]

Вторичные конечные точки (8)

• Toxicity of conditioning [Срок оценки: From HSCT to the follow-up assessment at 28 days and 100 days post-treatment.]
• Engraftment [Срок оценки: Platelet engraftment was assessment at 28 days post-transplantation.]
• GVHD [Срок оценки: From HSCT to the follow-up assessment at 12 months post-treatment.]
• Overall Survival [Срок оценки: From HSCT to the follow-up assessment at 12 months post-treatment.]
• Cumulative Incidence of Relapse [Срок оценки: From HSCT to the follow-up assessment at 12 months post-treatment.]
• Leukemia-free survival [Срок оценки: From HSCT to the follow-up assessment at 12 months post-treatment.]
• Event-Free Survival [Срок оценки: From HSCT to the follow-up assessment at 12 months post-treatment.]
• Viral Infection [Срок оценки: From HSCT to the follow-up assessment at 12 months post-treatment.]

Критерии участия

Критерии включения

\- (a)Diagnosed with AML in first complete remission (CR1). (b)Age ≥55 years. (c)Availability of an haploidentical donor, first transplant, no matched sibling or unrelated donor.

(d)Willingness to provide written informed consent.

Критерии исключения

• (a) Uncontrolled active infection. (b) Secondary AML. (c)Refusal to provide informed consent.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Peking University People's Hospital — Пекин

Публикации

• Santoro N, Labopin M, Ciceri F, Van Lint MT, Nasso D, Blaise D, Arcese W, Tischer J, Bruno B, Ehninger G, Koc Y, Santarone S, Huang XJ, Savani BN, Mohty M, Ruggeri A, Nagler A. Impact of conditioning intensity on outcomes of haploidentical stem cell transplantation for patients with acute myeloid leukemia 45 years of age and over. Cancer. 2019 May 1;125(9):1499-1506. doi: 10.1002/cncr.31941. Epub PMID 30620383
• Sun YQ, Xu LP, Zhang XH, Liu DH, Chen H, Wang Y, Yan CH, Wang JZ, Wang FR, Zhang YY, Liu KY, Huang XJ. A retrospective comparison of BU-fludarabine and BU-CY regimens in elderly patients or in patients with comorbidities who received unmanipulated haploidentical hematopoietic SCT. Bone Marrow Transplant. 2015 Apr;50(4):601-3. doi: 10.1038/bmt.2014.303. Epub 2015 Jan 19. No abstract available. PMID 25599162
• Huang XJ, Zhu HH, Chang YJ, Xu LP, Liu DH, Zhang XH, Jiang B, Jiang Q, Jiang H, Chen YH, Chen H, Han W, Liu KY, Wang Y. The superiority of haploidentical related stem cell transplantation over chemotherapy alone as postremission treatment for patients with intermediate- or high-risk acute myeloid leukemia in first complete remission. Blood. 2012 Jun 7;119(23):5584-90. doi: 10.1182/blood-2011-11-38 PMID 22535659
• Sun YQ, Han TT, Wang Y, Yan CH, Wang FR, Wang ZD, Kong J, Chen YH, Chen H, Han W, Chen Y, Zhang YY, Zhang XH, Xu LP, Liu KY, Huang XJ. Haploidentical Stem Cell Transplantation With a Novel Conditioning Regimen in Older Patients: A Prospective Single-Arm Phase 2 Study. Front Oncol. 2021 Feb 26;11:639502. doi: 10.3389/fonc.2021.639502. eCollection 2021. PMID 33718234

Идентификаторы

NCT: NCT06946602 · 2025PHB096-001 · Peking University

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗