BeFluBu vs FluBuRux Conditioning in Haploidentical HCT

Официальное название

Randomized Trial of Benadamustine Versus Ruxolitinib With Fludarabine and Busulfan Conditioning in Recipients of Haploidentical Stem Cell Transplantation

Обзор

Haploidentical hematopoietic stem cell transplantation irrespective of the conditioning intensity and graft-versus-host disease prophylaxis is associated with high frequency of primary and secondary graft failure. Different technologies of with replete or depleted graft are associated with 7-20% of graft failures in different diseases. Fludarabine and busulfan conditioning is the most commonly used approach for a variety of diseases. In two previously completed trials of addition of either bendamustine and ruxolitinib to conditioning we observed low rates of primary graft failure with both approaches. The study is the direct randomized comparisons of these two approaches with the primary aim of reducing composite events of primary graft failure, relapse and non-relapse mortality. The stratas for the study are Disease Risk Index (DRI) and the age of the haploidentical donor (\<35 vs ≥35).

Вмешательства

• Препарат Bendamustine Hydrochloride
  Days -7 through -6: Bendamustine 90 mg/m2 iv x 2 days
• Препарат Ruxolitinib
  Days -7 through -2: ruxolitinib 5 mg tid per os

Первичные конечные точки

• Event-free survival [Срок оценки: 2 years]

Вторичные конечные точки (9)

• Cumulative incidence of primary and secondary graft failure [Срок оценки: 365 days]
• Incidence of HSCT-associated adverse events (safety and toxicity) [Срок оценки: 125 days]
• Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence [Срок оценки: 100 days]
• Cumulative incidence of acute GVHD grade II-IV [Срок оценки: 125 days]
• Incidence of moderate and severe chronic GVHD [Срок оценки: 2 years]
• Non-relapse mortality analysis [Срок оценки: 2 years]
• Overall survival analysis [Срок оценки: 2 years]
• GVHD-relapse-free survival analysis [Срок оценки: 2 years]
• Relapse cumulative incidence analysis [Срок оценки: 2 years]

Критерии участия

Критерии включения

• Patients must have an indication for allogeneic hematopoietic stem cell transplantation with myeloablative conditioning for malignant disease
• Diagnosis: acute myeloid leukemia, acute lymphoblastic leukemia, mixed lineage acute leukemia, lymphoblastic lymphoma, chronic myeloid leukemia, myelodysplastic syndromes, myeloprolipherative neoplasm
• Age ≥18
• Malignant disease in hematologic response: <5% of clonal blasts in the bone marrow and no clonal blasts in peripheral blood.
• Patients with 5-9/10 HLA-matched related 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

Критерии исключения

• Titer of anti-donor anti-HLA antibodies ≥ 5000 at the time of inclusion
• Moderate or severe cardiac disease: ejection fraction <50%, unstable angina, stable angina NYHA class III or IV, chronic heart failure NYHA class III or IV, Lawn grade V arrhythmia, myocardial infarction within 3 months before inclusion
• Stroke within 3 months of inclusion, unless related to the underlying malignancy
• Severe decrease in pulmonary function: FEV1 <50% or DLCO<50% of predicted or respiratory distress or need for oxygen support;
• Severe organ dysfunction: AST or ALT >5 upper normal limits, bilirubin >1.5 upper normal limits, creatinine >2 upper normal limits
• Creatinine clearance < 40 mL/min
• Uncontrolled bacterial or fungal infection at the time of enrollment defined by CRP> 70 mg/L
• Requirement for vasopressor support at the time of enrollment
• Karnofsky index <70%
• Pregnancy
• Somatic or psychiatric disorder making the patient unable to sign informed consent

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

Россия · 1 центр

• RM Gorbacheva Research Institute — Saint Petersburg

Идентификаторы

NCT: NCT06477549 · 14/24-n

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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