Reduced Intensity Conditioning Regimens for Acute Myeloid Leukemia and Myelodysplastic Syndrome

February 5, 2025 updated by: Wuhan Union Hospital, China

Reduced Intensity Conditioning With Fludarabine and Busulfan Versus Fludarabine and Melphalan Before Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndrome: A Randomised, Multi-Center, Phase III Study

The goal of this clinical trial is to compare outcomes of two reduced intensity conditioning (RIC) regimens (fludarabine plus busulfan and fludarabine plus melphalan) in allogeneic hematopoietic stem cell transplantation (HSCT) for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) patients. The main questions it aims to answer are:

  • The safety of two reduced intensity conditioning (RIC) regimens (fludarabine plus busulfan and fludarabine plus melphalan) in allogeneic hematopoietic stem cell transplantation for adult AML/MDS patients with HCT-CI≥3 or aged ≥55 years.
  • The efficacy of two reduced intensity conditioning (RIC) regimens (fludarabine plus busulfan and fludarabine plus melphalan) in allogeneic hematopoietic stem cell transplantation for adult AML/MDS patients with HCT-CI≥3 or aged ≥55 years.

Participants will be randomized to one of two reduced intensity conditioning (RIC) regimens (fludarabine plus busulfan and fludarabine plus melphalan)

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

Detailed Description

Patients are randomized to one of two reduced intensity conditioning (RIC) regimens: the combination of fludarabine (30 mg/m^2/day, days -6 to days -2, the total dase is 150 mg/m^2) and busulfan (3.2 mg/kg/day, days -3 to days -2, the total dose is 6.4 mg/kg) (Flu/Bu) or fludarabine (30 mg/m^2/day, days -6 to days -2, the total dose is 150 mg/m^2) and melphalan (70 mg/m^2/day, days -3 to days -2, the total dose is 140 mg/m^2) (Flu/Mel). A total of 200 patients (100 to each arm) will be recruited in this study over a period of two years. Patients will be followed for up to 18 months from allogeneic hematopoietic stem cell transplantation.

Study Type

Interventional

Enrollment (Estimated)

200

Phase

  • Phase 3

Contacts and Locations

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

Study Locations

  • China
    • Hubei
      • Wuhan, Hubei, China, 430000
        • Wuhan Union Hospital, Tongji Medical college, Huazhong University of Science and Technology

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age equal or more than 18 years old.
  • Patients diagnosed with AML or MDS.
  • Patients who have related or unrelated bone marrow or peripheral blood donors and plan to undergo hematopoietic stem cell transplantation.
  • Hct-specific complication index score (HCT-CI) more than or equal to 3 or the age of Patients ≥55 years.
  • Sign the informed consent, promise to abide by the research procedures, and cooperate with the implementation of the whole process of the research.

Exclusion Criteria:

  • Patients with central nervous system involvement.
  • Patients with HIV seropositive.
  • Patients with other serious diseases and a life expectancy of less than six months
  • Patients with severe mental or psychological disorders.
  • Patients without written informed consent.

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: fludarabine and busulfan
fludarabine (30 mg/m^2/day, days -6 to days -2, the total dase is 150 mg/m^2) and busulfan (3.2 mg/kg/day, days -3 to days -2, the total dose is 6.4 mg/kg)
Drug: Fludarabine and Busulfan
Fludarabine with total dose of 150 mg/m^2 in combination with Busulfan with total dose of 6.4 mg/kg
Other Names:
  • Fludara and Busulfex
Experimental: fludarabine and melphalan
fludarabine (30 mg/m^2/day, days -6 to days -2, the total dose is 150 mg/m^2) and melphalan (70 mg/m^2/day, days -3 to days -2, the total dose is 140 mg/m^2)
Drug: Fludarabine and Melphalan
Fludarabine with total dose of 150 mg/m^2 in combination with Melphalan with total dose of 140 mg/m^2
Other Names:
  • Busulfex and Fludara

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS)
Time Frame: 18 months post-randomization
Survival without relapse or progression of the primary disease. Kaplan-Meier (KM) method was used to estimate median PFS.
18 months post-randomization

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: 18 months post-randomization
Overall survival is defined as survival duration from the date of randomization to the date of death from any cause. Kaplan-Meier (KM) method was used to estimate median OS
18 months post-randomization
Non-Relapse Mortality (NRM)
Time Frame: 18 months post-randomization
Death not due to recurrence or progression of the primary disease. Recurrence was considered as a competing risk event, and the Gray test was used for statistical analysis.
18 months post-randomization
Disease Relapse
Time Frame: 18 months post-randomization
Relapse of the primary disease. Non-relapse mortality (TRM) was considered as a competing risk event, and Gray's test was used for statistical analysis.
18 months post-randomization
Percentage of Participants With Severe Acute Graft-versus-host Disease (GVHD)
Time Frame: Day 100 post-transplant

Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995:

Skin stage:

0: No rash

Rash <25% of body surface area Rash on 25-50% of body surface area Rash on > 50% of body surface area Generalized erythroderma with bullous formation

Liver stage (based on bilirubin level)*:

0: <2 mg/dL

2-3 mg/dL 3.01-6 mg/dL 6.01-15.0 mg/dL >15 mg/dL

GI stage*:

0: No diarrhea or diarrhea <500 mL/day

Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD Diarrhea 1000-1499 mL/day Diarrhea >1500 mL/day Severe abdominal pain with or without ileus * If multiple etiologies are listed for liver or GI, the organ system is downstaged by 1.

GVHD grade:

0: All organ stages 0 or GVHD not listed as an etiology I: Skin stage 1-2 and liver and GI stage 0 II: Skin stage 3 or liver or GI stage 1 III: Liver stage 2-3 or GI stage 2-4 IV: Skin or liver stage 4
Day 100 post-transplant
Percentage of Participants With Chronic GVHD
Time Frame: 18 months post-transplant
Chronic GVHD is classified as the occurrence of mild, moderate, or severe chronic GVHD per 2005 NIH Consensus Criteria (Filipovich et al. 2005)
18 months post-transplant

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Neutrophil and Platelet Engraftment
Time Frame: Days 7 to 60 post-transplant
Neutrophil engraftment is defined as achieving an absolute neutrophil count greater than 500x10^6/liter for 3 continuous measurements on different days. The first of the 3 days will be labeled as the day of neutrophil engraftment. Platelet engraftment is defined as achieving platelet counts greater than 20,000/microliter for continuous measurements over 7 days without requiring platelet transfusions. The first day of the 7 days will be marked as the day of platelet engraftment.
Days 7 to 60 post-transplant
Incidence and Percentage of Severe Infection
Time Frame: 18 months post-transplant
List the type, number, and severity of infection events
18 months post-transplant
Percentage of Participants With Toxicities
Time Frame: Days 1 to 60 post-transplant
The severity of oral ulcer or diarrhea in the early stage after transplantation, clinically significant abnormal laboratory findings.
Days 1 to 60 post-transplant
Number of Lymphocyte Subsets
Time Frame: Days 28, days 60, 3 months post-transplant, 6 months post-transplant, 12months post-transplant, 18 months post-transplant
Number of Lymphocyte Subsets of Participants
Days 28, days 60, 3 months post-transplant, 6 months post-transplant, 12months post-transplant, 18 months post-transplant

Collaborators and Investigators

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

Sponsor

Wuhan Union Hospital, China

Investigators

  • Study Chair: Linghui Xia, Professor, Department of Hematology, Wuhan Union Hospital, Tongji Medical college, Huazhong University of Science and Technology

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)

February 15, 2023

Primary Completion (Estimated)

December 30, 2025

Study Completion (Estimated)

December 30, 2025

Study Registration Dates

First Submitted

December 30, 2022

First Submitted That Met QC Criteria

January 5, 2023

First Posted (Actual)

January 6, 2023

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 5, 2025

Last Verified

October 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • WHUH-RIC-HSCT-1115

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

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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