Acute Myeloid Leukemia (AML), Allogeneic Hematopoietic Stem Cell Transplantation Recipient
Conditions
Keywords
Acute Myeloid Leukemia; Elderly; Hematopoietic Stem Cell Transplantation; Venetoclax; Busulfan; Preconditioning
Brief summary
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.
Interventions
DRUGVaBU
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.
Sponsors
The First Affiliated Hospital of Soochow University
Suzhou Hongci Hematology Hospital, Suzhou, China
Huai'an Second People's Hospital and the Affiliated Huai'an Hospital of Xuzhou Medical University
Shenzhen People's Hospital
Henan Cancer Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
All enrolled participants receive the same VABu conditioning regimen (Venetoclax, Azacitidine, Semustine, Cytarabine and Busulfan) prior to allogeneic hematopoietic stem cell transplantation. No comparator or control group is included.
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | 1 year and 2 years post-transplantation | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 1 year and 2 years post-transplantation | 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. |
| Cumulative Incidence of Relapse (CIR) | 1 year, 2 years | — |
| Non-relapse Mortality (NRM) | Day 100, 1 year, 2 years | — |
| GVHD-free Relapse-free Survival (GRFS) | 1 year, 2 years | — |
| Incidence of Acute GVHD | Day 100, Day 180 | — |
| Incidence of Chronic GVHD | 1 year, 2 years | — |
| CMV Reactivation Rate | 1 year | — |
| EBV Reactivation Rate | 1 year | include EBV-related post-transplant lymphoproliferative disorder (PTLD) |
| Engraftment Rate | Day 30 | — |
| Safety and Tolerability (TEAEs) | Treatment period to 30 days post-treatment | — |
Countries
China
Contacts
CONTACTHuiying Qiu, M.D.
Outcome results
None listed