VABu Conditioning in Elderly AML HSCT

Официальное название

Efficacy and Safety of the VABu Conditioning Regimen in Elderly Patients With Acute Myeloid Leukemia Undergoing Hematopoietic Stem Cell Transplantation: An Open-Label, Multicenter, Single-Arm Clinical Study

Обзор

This is an open-label, multi-center, single-arm clinical study evaluating the efficacy and safety of the VABu conditioning regimen in elderly patients (≥60 years) with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (HSCT). The VABu regimen consists of Venetoclax, Azacitidine, Semustine, Cytarabine, and Busulfan. All enrolled participants will receive the VABu regimen as conditioning therapy prior to HSCT. The study aims to enroll 20 participants from multiple centers in China. The primary objectives are to evaluate the overall response rate, cumulative relapse rate, overall survival, graft-versus-host disease (GVHD)-free relapse-free survival (GRFS), non-relapse mortality (NRM), incidence of acute and chronic GVHD, and reactivation rates of cytomegalovirus (CMV) and Epstein-Barr virus (EBV). Safety outcomes include treatment-related toxicities, such as bone marrow suppression, infection, and organ dysfunction.

Вмешательства

• Препарат VaBU
  The VABu conditioning regimen is administered prior to allogeneic hematopoietic stem cell transplantation (HSCT). The regimen consists of the following drugs administered sequentially: Venetoclax: 600 mg/m² orally once daily on days -10 to -5. Azacitidine: 75 mg/m² subcutaneously once daily on days -10 to -6. Semustine: 250 mg/m² orally once on day -10. Cytarabine: 2 g/m² intravenously once daily on day -1. Busulfan: 0.8 mg/kg intravenously every 6 hours on days -4 to -2 (total of 12 doses). T

Первичные конечные точки

• Progression-Free Survival (PFS) [Срок оценки: 1 year and 2 years post-transplantation]

Вторичные конечные точки (10)

• Overall Survival (OS) [Срок оценки: 1 year and 2 years post-transplantation]
• Cumulative Incidence of Relapse (CIR) [Срок оценки: 1 year, 2 years]
• Non-relapse Mortality (NRM) [Срок оценки: Day 100, 1 year, 2 years]
• GVHD-free Relapse-free Survival (GRFS) [Срок оценки: 1 year, 2 years]
• Incidence of Acute GVHD [Срок оценки: Day 100, Day 180]
• Incidence of Chronic GVHD [Срок оценки: 1 year, 2 years]
• CMV Reactivation Rate [Срок оценки: 1 year]
• EBV Reactivation Rate [Срок оценки: 1 year]
• Engraftment Rate [Срок оценки: Day 30]
• Safety and Tolerability (TEAEs) [Срок оценки: Treatment period to 30 days post-treatment]

Критерии участия

Критерии включения

• Age ≥ 60 years.
• Confirmed diagnosis of acute myeloid leukemia (AML) according to WHO classification, with intermediate or high-risk prognosis.
• Previous response to Venetoclax-based therapy.
• Planned to undergo allogeneic hematopoietic stem cell transplantation (HSCT).
• Donor availability: Related donor matched at least 5/10 at HLA-A, -B, -C, -DQB1, and -DRB1; OR unrelated donor matched at least 8/10 at the same loci.
• Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) score ≤ 4.
• ECOG performance status 0-2.
• Adequate organ function as defined by: Creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 45 mL/min (Cockcroft-Gault formula or 24-hour urine collection)； AST ≤ 3.0 × ULN and ALT ≤ 3.0 × ULN； Total bilirubin ≤ 1.5 × ULN； Left ventricular ejection fraction (LVEF) > 50%； Baseline oxygen saturation > 92%； DLCO ≥ 40% and FEV1 ≥ 50%；
• Ability to understand and provide written informed consent.

Критерии исключения

• Age < 60 years.
• Poor response to prior Venetoclax-based therapy.
• Unstable systemic disease (unstable angina, myocardial infarction, cerebrovascular accident within 3 months; NYHA Class III-IV heart failure; severe arrhythmia; pulmonary hypertension).
• Active uncontrolled infection or active bleeding in vital organs.
• CNS symptoms grade ≥ 2 requiring treatment.
• Major organ surgery within 6 weeks.
• History of malignant disease other than AML within 5 years.
• History of thrombosis, embolism, or cerebral hemorrhage within 1 year.
• ECOG performance status > 2.
• HCT-CI score > 4.
• Organ failure meeting specified criteria.
• Known HIV, active HBV, or active HCV infection.
• History of autoimmune disease requiring systemic immunosuppressive therapy.
• Pregnancy, breastfeeding, or unwillingness to use effective contraception in patients of childbearing potential.
• Drug abuse or chronic alcoholism.
• Psychiatric disorder or other condition compromising informed consent or compliance.
• Any other condition making the patient unsuitable for study participation in the investigator's judgment.

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

Китай · 1 центр

• The First Affiliated Hospital of Soochow University — Сучжоу

Идентификаторы

NCT: NCT07583888 · ZSQ003

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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