Leukemia, Myeloid, Acute(AML), Hematopoietic Stem Cell Transplantation (HSCT)
Conditions
Keywords
Acute Myeloid Leukemia, Allogeneic Hematopoietic Stem Cell Transplantation, Conditioning Regimen, Venetoclax, Azacitidine, VABu, Low Performance Status, High Comorbidity Index, Single-Arm Study, Prospective Study, AML, Allo-HSCT
Brief summary
This study evaluates the effectiveness and safety of a new conditioning regimen called VABu before stem cell transplantation in patients with acute myeloid leukemia (AML) who are in their first complete remission (CR1), classified as non-high-risk per ELN 2022 guidelines, but have poor physical condition (ECOG performance status ≥ 2) or high comorbidity burden (HCT-CI ≥ 2). VABu combines venetoclax, azacitidine (or decitabine as an alternative), and busulfan. This is a single-arm, prospective study with 42 participants. All participants will receive the VABu regimen followed by stem cell transplantation. The primary outcome measure is 2-year overall survival (OS). Secondary outcomes include 2-year relapse-free survival (RFS), transplant-related mortality (TRM), engraftment failure rate, bloodstream infection (BSI), and 2-year all-cause mortality and non-relapse mortality (NRM). The study is conducted at the First Affiliated Hospital of Soochow University.
Detailed description
Acute myeloid leukemia (AML) is the most common acute leukemia in adults. For patients who are unfit for intensive chemotherapy due to poor performance status or high comorbidity burden, allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only potential curative treatment. However, these patients often have low transplantation rates and suboptimal outcomes with reduced-intensity conditioning regimens. Venetoclax combined with azacitidine has been established as the standard of care for unfit AML patients, demonstrating high remission rates and good tolerability. Building on this, our center has previously explored the VABu regimen (venetoclax, azacitidine, and busulfan) as a conditioning therapy in elderly AML patients undergoing allo-HSCT, with preliminary results showing reduced chemotherapy-related toxicity and a 2-year overall survival rate of approximately 70%. This is a single-arm, prospective, single-center study. A total of 42 participants will be enrolled. Eligible participants are patients aged 18 to 70 years with non-APL AML who have achieved first complete remission (CR1), are classified as non-high-risk per ELN 2022 guidelines, and have either ECOG performance status ≥ 2 (not due to leukemia) or HCT-CI ≥ 2. All participants will receive the VABu conditioning regimen followed by allo-HSCT. The VABu regimen consists of venetoclax 600 mg/m² once daily on days -12 to -7, azacitidine 75 mg/m² once daily on days -11 to -7 (or decitabine 20 mg/m² for 5 days), cytarabine 2.0 g/m² every 12 hours on day -6, busulfan 0.8 mg/kg every 6 hours on days -5 to -3, and antithymocyte globulin (ATG) at 2.5 mg/kg/day according to donor type (haploidentical/unrelated donors on days -5 to -2, or matched sibling donors on days -3 to -2). Hematopoietic stem cell infusion occurs on day 0, followed by standard graft-versus-host disease (GVHD) prophylaxis. The primary outcome measure is 2-year overall survival (OS). Secondary outcome measures include 2-year relapse-free survival (RFS), transplant-related mortality (TRM), engraftment failure rate, bloodstream infection (BSI), and 2-year all-cause mortality and non-relapse mortality (NRM). Safety will be monitored through adverse event collection and grading per CTCAE 5.0 criteria. Follow-up assessments are scheduled at weeks 1, 2, 3, 4, and months 2, 3, 6, 12 post-transplantation. The study period is from August 2026 to July 2029. Statistical analyses will be performed using SPSS and R, with Kaplan-Meier method for OS, and Cox regression and logistic regression for multivariate analyses.
Interventions
DRUGVenetoclax
Venetoclax 600 mg/m² administered orally once daily on days -12 to -7 as part of the VABu conditioning regimen for allogeneic hematopoietic stem cell transplantation. Venetoclax is a selective BCL-2 inhibitor used to enhance anti-leukemic activity.
DRUGAzacitidine (AZA)
Azacitidine 75 mg/m² administered subcutaneously once daily on days -11 to -7 as part of the VABu conditioning regimen. This is one of the two optional hypomethylating agents; the alternative is decitabine 20 mg/m² for 5 days. Azacitidine has synergistic anti-leukemic effects when combined with venetoclax.
Decitabine 20 mg/m² administered intravenously once daily for 5 days on days -11 to -7 as an alternative to azacitidine in the VABu conditioning regimen. This is one of the two optional hypomethylating agents; the alternative is azacitidine 75 mg/m² once daily. Decitabine has synergistic anti-leukemic effects when combined with venetoclax.
Cytarabine 2.0 g/m² administered intravenously every 12 hours on day -6 as part of the VABu conditioning regimen. Intermediate-dose cytarabine is used to further eliminate minimal residual disease prior to hematopoietic stem cell infusion.
DRUGBusulfan (BU)
Busulfan 0.8 mg/kg administered intravenously every 6 hours on days -5 to -3 as part of the VABu conditioning regimen. Busulfan is an alkylating agent used at reduced intensity to achieve sufficient anti-leukemic effect while minimizing organ toxicity.
Antithymocyte globulin (ATG) 2.5 mg/kg/day administered intravenously once daily for graft-versus-host disease (GVHD) prophylaxis. Haploidentical or unrelated donors: ATG given on days -5 to -2 (4 doses). Matched sibling donors: ATG given on days -3 to -2 (2 doses).
Sponsors
The First Affiliated Hospital of Soochow University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18 to 70 years. 2. Diagnosis of acute myeloid leukemia (AML) other than acute promyelocytic leukemia (APL), with first complete remission (CR1) achieved after induction chemotherapy. 3. Classified as non-high-risk per ELN 2022 risk stratification guidelines. 4. ECOG performance status ≥ 2 (not due to leukemia) OR Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) ≥ 2. 5. Willing to undergo allogeneic hematopoietic stem cell transplantation and has a suitable donor. 6. Voluntarily signs informed consent form after full understanding of the study.
Exclusion criteria
1. Allergy to any component of the study drugs. 2. Psychiatric or psychological disorders that prevent cooperation with treatment. 3. Uncontrolled systemic or local severe infection. 4. Severe dysfunction of major organs (heart, lung, liver, kidney) that, in the investigator's opinion, makes the patient unsuitable for enrollment. 5. Currently participating in or planning to participate in any other clinical study. 6. Any other conditions that, in the investigator's opinion, make the patient unsuitable for enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 2-Year Overall Survival (OS) | 2 years | Overall survival is defined as the time from enrollment to death from any cause. Participants alive at the end of follow-up will be censored at their last known alive date. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 2-Year Relapse-Free Survival (RFS) | 2 years | Relapse-free survival is defined as the time from enrollment to the first occurrence of relapse or death from any cause, whichever occurs first. Participants alive and relapse-free at the end of follow-up will be censored at their last known disease-free date. Relapse is defined as disease recurrence confirmed by bone marrow morphology, cytogenetics, or molecular testing per ELN 2022 criteria. |
| 2-Year All-Cause Mortality, Transplant-Related Mortality (TRM), and Non-Relapse Mortality (NRM) | 2 years | All-cause mortality is defined as death from any cause within 2 years of enrollment. Transplant-related mortality (TRM) is defined as death from any cause other than disease relapse or progression, with a focus on transplant-related complications (e.g., infection, GVHD, organ toxicity). Non-relapse mortality (NRM) is defined as death from any cause other than disease relapse or progression, and will be reported as a competing risk for relapse outcomes. The cumulative incidences of TRM and NRM will be estimated separately, and all-cause mortality will be reported as the overall proportion of deaths. |
| Engraftment Failure Rate | Day 28 post-transplantation | Engraftment failure is defined as the failure to achieve neutrophil engraftment by day 28 post-transplantation. Neutrophil engraftment is defined as an absolute neutrophil count ≥ 0.5 × 10⁹/L for three consecutive days. The rate of engraftment failure will be reported as the proportion of participants who fail to achieve engraftment by day 28. |
| Bloodstream Infection (BSI) Rate | Day 28 post-transplantation | Bloodstream infection is defined as the occurrence of at least one positive blood culture for a bacterial or fungal pathogen during the peri-transplantation period. The BSI rate will be reported as the proportion of participants with at least one episode of bloodstream infection from transplantation to day 28 post-transplantation. |
Countries
China
Contacts
CONTACTDepei Wu, MD, PhD
Outcome results
None listed