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

August 22, 2024 updated by: He Huang

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

118

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310006
        • Recruiting
        • The First Affiliated Hospital of Zhejiang University school of medicine
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: VAA group
Drug: Venetoclax
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.
Active Comparator: HSCT group
Drug: Allogeneic transplant

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to 2 years
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.
Up to 2 years
2-years Relapse Rate
Time Frame: Up to 2 years
Relapse rate is defined as relapse probability at a given time point
Up to 2 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to 2 years
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.
Up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

He Huang

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 17, 2024

Primary Completion (Estimated)

December 30, 2027

Study Completion (Estimated)

February 28, 2028

Study Registration Dates

First Submitted

August 20, 2024

First Submitted That Met QC Criteria

August 22, 2024

First Posted (Actual)

August 26, 2024

Study Record Updates

Last Update Posted (Actual)

August 26, 2024

Last Update Submitted That Met QC Criteria

August 22, 2024

Last Verified

August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TROPHY-AML03

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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