RIC Allo-HSCT vs. Venetoclax-Based Consolidation in Elderly AML Patients After First CR

Trial Title: RIC Allo-HSCT vs. Venetoclax-Based Consolidation in Elderly AML Patients After First CR

NCT ID: NCT06571825

Condition: Acute Myeloid Leukemia

Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Venetoclax

Conditions: Keywords:
elderly
AML
venetoclax
allo-HSCT

Study type: Interventional

Study phase: Phase 4

Overall status: Recruiting

Study design:

Allocation: Non-Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Venetoclax
Description: The consolidation therapy involves a regimen of intermediate-dose cytarabine (Ara-C) combined with Ven, specifically Ara-C at 1.0 g/m²/day for 3 days (days 1-3) and Ven at 400 mg/day for 10 to 14 days (days 1-10 to 14), with each cycle lasting 4 to 6 weeks, for a total of 3 consolidation cycles. This is followed by maintenance therapy with azacitidine (AZA) at 50 mg/m²/day for 5 days (days 1-5), with each cycle lasting 4 weeks, for a total of 6 maintenance cycles.
Arm group label: VAA group

Intervention type: Drug
Intervention name: Allogeneic transplant
Description: The consolidation therapy involves allo-HSCT, with the choice of conditioning regimens typically using reduced-intensity conditioning such as the Fludarabine+Busulfan (FluBu) or Fludarabine+Melphalan (FluMel) regimens commonly used by centers, which can also include Ven. FluBu regimen: Flu 30 mg/m²/day from day -10 to day -5, Bu 3.2 mg/kg/day from day -6 to day -5 or day -7 to day -5, antithymocyte globulin (ATG) (e.g., rabbit ATG at a total dose of 6-7.5 mg/kg, administered from day -4 to day -1), and Ven from day -10 to day -4. FluMel regimen: Flu 30 mg/m²/day from day -10 to day -5, Mel 50-70 mg/m²/day from day -4 to day -3, ATG and Ven from day -10 to day -4. 12 weeks (±4 weeks) post-HSCT maintenance begins with AZA at 32 mg/m²/day for 5 days (days 1-5), with each lasting 6 weeks, for a total of 6 cycles. Donor lymphocyte infusion is allowed in cases of minimal residual disease (MRD) positivity.
Arm group label: HSCT group

Summary: Elderly patients with acute myeloid leukemia (AML) often face unfavorable prognostic factors such as multiple comorbidities, adverse cytogenetic profiles, and pre-existing hematological disorders. The long-term survival rate remains very low, with a 5-year survival rate of only 5% to 10%. The introduction of the BCL-2 inhibitor venetoclax (Ven) has improved the induction remission rates in elderly patients. However, the question of whether to use chemotherapy maintenance or proceed with allogeneic hematopoietic stem cell transplantation (allo-HSCT) for post-remission consolidation therapy remains unclear due to the lack of prospective controlled studies. Therefore, our center plans to conduct a prospective, open-label, two-arm, non-randomized, single-center study to further explore the optimal consolidation treatment strategy for elderly AML patients at intermediate and high risk following induction complete remission (CR).

Criteria for eligibility:
Criteria:
Inclusion Criteria: - Diagnosed with AML according to the 2022 WHO diagnostic criteria; - Age 60-75 years; - Intermediate to high-risk AML according to the ELN criteria, AML with myelodysplasia-related changes (AML-MRC) or therapy-related AML (t-AML), or core-binding factor AML (CBF-AML) with D816 KIT mutation; or newly diagnosed hypercellular leukemia (WBC ≥ 10×10^9/L); - Achieved CR or CR with incomplete hematologic recovery (CRi) after one to two courses of induction chemotherapy; - Have a matched related, haploidentical, or mismatched unrelated hematopoietic stem cell donor; - Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2; Creatinine clearance ≥ 60 mL/min (calculated using the Cockcroft-Gault formula); - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3× the upper limit of normal (ULN), and total bilirubin ≤ 2× ULN; - Echocardiography (ECHO) showing left ventricular ejection fraction (LVEF) ≥ 50%; Expected survival > 8 weeks; - Voluntarily signed the informed consent form and can understand and comply with the study's requirements. Exclusion Criteria: - Currently has clinically active cardiovascular disease, such as uncontrolled arrhythmias, uncontrolled hypertension, congestive heart failure, any class 3 or 4 heart disease according to the New York Heart Association (NYHA) functional classification, or a history of myocardial infarction within 3 months before screening; - Other severe diseases that may limit the patient's participation in this trial (e.g., severe infection, renal failure); - Known human immunodeficiency virus (HIV) infection or severe viral hepatitis not controlled by medication; - Pregnant or breastfeeding women; - Unable to understand, comply with the study protocol, or unable to sign the informed consent form.

Gender: All

Minimum age: 60 Years

Maximum age: 75 Years

Healthy volunteers: No

Locations:

Facility:
Name: The First Affiliated Hospital of Zhejiang University School of Medicine

Address:
City: Hangzhou
Zip: 310006
Country: China

Status: Recruiting

Contact:
Last name: Yanmin Zhao, PhD

Phone: +8615858199217
Email: zjzhaoyanmin@163.com

Start date: July 17, 2024

Completion date: February 28, 2028

Lead sponsor:
Agency: He Huang
Agency class: Other

Source: Zhejiang University

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06571825