VABu Conditioning in Elderly AML HSCT

Phase 3RecruitingNCT07583888

The First Affiliated Hospital of Soochow University20 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Allogeneic Hematopoietic Stem Cell Transplantation Recipient Acute Myeloid Leukemia (AML)

Interventions

VaBUDRUG

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). The conditioning regimen is completed before HSCT. Dose adjustments may be made based on toxicity, concomitant medications (especially CYP3A4 inhibitors), and individual patient tolerance.

Eligibility

Sex: ALLMin age: 60 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age ≥ 60 years. 2. Confirmed diagnosis of acute myeloid leukemia (AML) according to WHO classification, with intermediate or high-risk prognosis. 3. Previous response to Venetoclax-based therapy. 4. Planned to undergo allogeneic hematopoietic stem cell transplantation (HSCT). 5. 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. 6. Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) score ≤ 4. 7. ECOG performance status 0-2. 8. 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%； 9. Ability to understand and provide written informed consent. Exclusion Criteria: 1. Age \< 60 years. 2. Poor response to prior Venetoclax-based therapy. 3. Unstable systemic disease (unstable angina, myocardial infarction, cerebrovascular accident within 3 months; NYHA Class III-IV heart failure; severe arrhythmia; pulmonary hypertension). 4. Active uncontrolled infection or active bleeding in vital organs. 5. CNS symptoms grade ≥ 2 requiring treatment. 6. Major organ surgery within 6 weeks. 7. History of malignant disease other than AML within 5 years. 8. History of thrombosis, embolism, or cerebral hemorrhage within 1 year. 9. ECOG performance status \> 2. 10. HCT-CI score \> 4. 11. Organ failure meeting specified criteria. 12. Known HIV, active HBV, or active HCV infection. 13. History of autoimmune disease requiring systemic immunosuppressive therapy. 14. Pregnancy, breastfeeding, or unwillingness to use effective contraception in patients of childbearing potential. 15. Drug abuse or chronic alcoholism. 16. Psychiatric disorder or other condition compromising informed consent or compliance. 17. Any other condition making the patient unsuitable for study participation in the investigator's judgment.

Outcomes

Primary Outcomes

Progression-Free Survival (PFS)

Progression-free survival is defined as the time from the date of transplantation to the date of disease progression, relapse, or death from any cause, whichever occurs first. Participants who are alive without progression or relapse at the last follow-up are censored.

Time frame: 1 year and 2 years post-transplantation

Secondary Outcomes

Overall Survival (OS)

Overall survival is defined as the time from the date of transplantation to the date of death from any cause. Participants who are alive at the last follow-up are censored.

Time frame: 1 year and 2 years post-transplantation

Cumulative Incidence of Relapse (CIR)

Time frame: 1 year, 2 years

Non-relapse Mortality (NRM)

Time frame: Day 100, 1 year, 2 years

GVHD-free Relapse-free Survival (GRFS)

Time frame: 1 year, 2 years

Incidence of Acute GVHD

Time frame: Day 100, Day 180

Incidence of Chronic GVHD

Time frame: 1 year, 2 years

CMV Reactivation Rate

Time frame: 1 year

EBV Reactivation Rate

include EBV-related post-transplant lymphoproliferative disorder (PTLD)

Time frame: 1 year

Engraftment Rate

Time frame: Day 30

Safety and Tolerability (TEAEs)

Time frame: Treatment period to 30 days post-treatment

VABu Conditioning in Elderly AML HSCT

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts