Optimization of Post-transplantation Benadamustine and Cyclophosphamide in Patients With High-risk Myeloid Malignancies and a Partially Mismatched Donor

Официальное название

Optimization of Post-transplantation Benadamustine and Cyclophosphamide in Patients With High-risk Myeloid Malignancies and a Partially Mismatched Donor (APTBCy)

Обзор

Optimization of bendamustine-containg graft-versus-host disease (GVHD) prophylaxis to reduce the incidence of secondary haemophagocytic lymphohistiocytosis and GVHD

Подробное описание

Prognosis of patients undergoing allogeneic stem cell transplantation (HCT) for high-risk myeloid malignancies, including refractory acute myeloid leukemia, with standard HCT technologies have relatively poor prognosis with 10-30% long-term disease-free survival. One of the approaches to augment graft-versus-leukemia effect the use of post-transplantation bendamustine in graft-versus-host disease prophylaxis. Despite high frequency of responses and durable remissions after this approach majority of patients develop a serious complication - cytokine release syndrome, which can be life-threatening in some patients. The combination bendamustine (PTB) and post-transplantation cyclophosphamide (PTCY) facilitates comparable graft-versus leukemia effect to PTB, but with better safety profile and reduced incidence of severe cytokine release syndrome.

Вмешательства

• Препарат Ruxolitinib
  ; Days -1 through +21: ruxolitinib 10 mg/kg/day p.o.
• Препарат Abatacept (Orencia)
  Days -1,+5, +14, +21 abatacept 10 mg/kg/day i.v.

Первичные конечные точки

• Overall survival analysis [Срок оценки: 2 years]

Вторичные конечные точки (9)

• Incidence of secondary hemophagocytic lymphohistiocytosis [Срок оценки: 100 days]
• Incidence of HSCT-associated adverse events (safety and toxicity) [Срок оценки: 100 days]
• Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence [Срок оценки: 100 days]
• Incidence of acute GVHD grade II-IV [Срок оценки: 180 days]
• Incidence of moderate and severe chronic GVHD [Срок оценки: 2 years]
• Non-relapse mortality analysis [Срок оценки: 2 years]
• Relapse rate analysis [Срок оценки: 2 years]
• Event-free survival analysis [Срок оценки: 2 years]
• GVHD-event-free survival analysis [Срок оценки: 2 years]

Критерии участия

Критерии включения

• Patients with indication for allogeneic hematopoietic stem cell transplantation
• Patients with <10/10 HLA-matched related or unrelated donor available. The donor and recipient must be identical by the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1, and HLA-DQB1.
• Peripheral blood stem cells or bone marrow as a graft source
• Diagnosis:

Acute myeloid leukemia Chronic myeloid leukemia, Ph+ Myelodysplastic Syndromes Myeloprolipherative neoplasms - High-risk disease defined as: Acute myeloid leukemia: >5% of clonal blasts in bone marrow despite adequate previous induction therapy or allogeneic stem cell transplantation Myelodysplastic Syndrome: >5% of blasts despite previous therapy Myeloid malignancy with with -7 or complex karyotype, or p53 mutation regardless of blast count in bone marrow Treatment-related myelodysplastic syndrome Second or subsequent allogeneic HCT after relapse of a myeloid malignancy Chronic myelomonocytic leukemia Myeloprolipherative neoplasms, unclassifiable

\- No severe concurrent illness

Критерии исключения

• Patients with indication for allogeneic hematopoietic stem cell transplantation
• Patients with <10/10 HLA-matched related or unrelated donor available. The donor and recipient must be identical by the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1, and HLA-DQB1.
• Peripheral blood stem cells or bone marrow as a graft source
• Diagnosis:

Acute myeloid leukemia Chronic myeloid leukemia, Ph+ Myelodysplastic Syndromes Myeloprolipherative neoplasms - High-risk disease defined as: Acute myeloid leukemia: >5% of clonal blasts in bone marrow despite adequate previous induction therapy or allogeneic stem cell transplantation Myelodysplastic Syndrome: >5% of blasts despite previous therapy Myeloid malignancy with with -7 or complex karyotype, or p53 mutation regardless of blast count in bone marrow Treatment-related myelodysplastic syndrome Second or subsequent allogeneic HCT after relapse of a myeloid malignancy Chronic myelomonocytic leukemia Myeloprolipherative neoplasms, unclassifiable

\- No severe concurrent illness

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Россия · 1 центр

• Pavlov University — Saint Petersburg

Публикации

• Moiseev I, Bondarenko S, Vlasova Y, Morozova E, Smirnova A, Epifanovskaya O, Zhogolev D, Chernishova D, Meliboev A, Khudayberdiev J, Mazing A, Lapin S, Kholopova I, Botina A, Baykov V, Popova M, Kosarev O, Kulagin A. Allogeneic hematopoietic cell transplantation with a combination of posttransplantation bendamustine and cyclophosphamide in refractory myeloid neoplasms. Cancer. 2025 May 15;131(10): PMID 40372957

Идентификаторы

NCT: NCT07238712 · 30/25-n

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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