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

ConditionAcute Myeloid Leukemia

Trial statusRecruiting

Trial phasePhase 4

Trial typeInterventional

Biological sexAll

Age60-75

SponsorHe Huang

About this trial

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).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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;

Disqualifiers

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;

Trial design

Design model

Parallel

Treatments tested in this trial

Venetoclax
Drug
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.
Allogeneic transplant
Drug
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.

Treatment groups

118 Participants

are divided into 2 treatment groups

Group A: VAA groupExperimental treatment 1 intervention

Group B: HSCT groupActive comparator 1 intervention

Trial outcomes

Primary outcomes

Relapse-free survival

Relapse-free survival (RFS) is measured from the date of achievement of first remission until the date of hematologic relapse or death from any cause.

Time frame

Up to 2 years

Secondary outcomes

Non-Relapsed Mortality

Non-relapsed mortality (NRM) is measured from the date of achievement of first remission until the date of death from any cause other than relapse.

Time frame

Up to 2 years

Overall Survival

OS is measured from the date of reaching CR1 to the date of death from any cause.

Time frame

Up to 2 years

2-years Relapse Rate

Relapse rate is defined as relapse probability at a given time point

Time frame

Up to 2 years

Other outcomes

Minimal Residual Disease (MRD) Detected by Flow Cytometry

Research on MRD involves using flow cytometry to detect residual cancer cells, with statistical methods including Kaplan-Meier survival analysis, Fine-Gray analysis and Cox regression modeling to evaluate disease remission and predict relapse risk.

Time frame

Up to 2 years

Number of Participants With Treatment-Related Adverse Events (AEs) as Assessed by CTCAE v5.0

Research on AE uses descriptive statistics, Kaplan-Meier survival analysis, χ² or Fisher's exact tests to assess and compare AE incidence and survival outcomes.

Time frame

Up to 2 years

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

He Huang

Lead sponsor

Zhejiang University

Sponsor institution

Source ClinicalTrials.gov

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