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NCT Number: NCT05674539

Reduced Intensity Conditioning Regimens for Acute Myeloid Leukemia and Myelodysplastic Syndrome

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)

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Key information

Conditions

Acute Myeloid Leukemia, Adult Allogeneic Hematopoietic Stem Cell Transplantation Bone Marrow Diseases Hematologic Diseases Hemic and Lymphatic Diseases Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Myelodysplastic Syndrome(MDS) Myelodysplastic Syndromes Neoplasms Neoplasms by Histologic Type

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Wuhan Union Hospital, Tongji Medical college, Huazhong University of Science and Technology

Wuhan, Hubei, 430000, China

About this study

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.

Who can participate

Healthy volunteers accepted: No

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

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.

Treatment and study plan

Fludarabine and Busulfan

Drug

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

Fludarabine and Melphalan

Drug

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

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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)

Other outcomes

  1. 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.

  2. Incidence and Percentage of Severe Infection

    Time frame: 18 months post-transplant

    List the type, number, and severity of infection events

  3. 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.

  4. 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

Sponsors and collaborators

Lead sponsor

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Other

Registry information

Official study title

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

Important dates

Study start
2023
Primary completion
2025
Study completion
2025
First posted
Jan 6, 2023
Registry last updated
Feb 10, 2025

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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