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NCT Number: NCT06571825

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

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).

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Key information

Conditions

Acute Myeloid Leukemia Hematologic Diseases Hemic and Lymphatic Diseases Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Neoplasms Neoplasms by Histologic Type

Age range

60 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

The First Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310006, China

Location status: Recruiting

Location contact

Yanmin Zhao, PhD

CONTACT

[email protected]

+8615858199217

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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.

Primary outcomes

  1. Relapse-free survival

    Time frame: Up to 2 years

    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.

Secondary outcomes

  1. Non-Relapsed Mortality

    Time frame: Up to 2 years

    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.

  2. Overall Survival

    Time frame: Up to 2 years

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

  3. 2-years Relapse Rate

    Time frame: Up to 2 years

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

Other outcomes

  1. Minimal Residual Disease (MRD) Detected by Flow Cytometry

    Time frame: Up to 2 years

    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.

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

    Time frame: Up to 2 years

    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.

Study contacts

Contact information is provided by the study sponsor or research team.

Yanmin Zhao, PhD

CONTACT

[email protected]

15858199217

Sponsors and collaborators

Lead sponsor

He Huang

Other

Registry information

Official study title

Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation in Comparison to Consolidation Therapy Based Venetoclax for Elderly Patients With Acute Myeloid Leukemia After First CR

Important dates

Study start
2024
Primary completion
2027
Study completion
2028
First posted
Aug 26, 2024
Registry last updated
Aug 26, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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