Clinical trial NCT05674539: Reduced Intensity Conditioning Regimens for Acute Myeloid Leukemia and Myelodysplastic Syndrome
Official 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
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE3
Conditions: Acute Myeloid Leukemia, Adult
Myelodysplastic Syndrome(MDS)
Allogeneic Hematopoietic Stem Cell Transplantation
Keywords: hematopoietic stem cell transplantation (HSCT)
reduced intensity conditioning (RIC)
Acute Myeloid Leukemia(AML)
Myelodysplastic Syndrome(MDS)
Lead sponsor: Wuhan Union Hospital, China
Sponsor class: OTHER
First posted: 2023-01-06
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized to one of two reduced intensity conditioning (RIC) regimens (fludarabine plus busulfan and fludarabine plus melphalan)
Primary purpose: TREATMENT

Brief summary: 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)

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: 18 months post-randomization
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: 18 months post-randomization
measure: Non-Relapse Mortality (NRM)
timeFrame: 18 months post-randomization
measure: Disease Relapse
timeFrame: 18 months post-randomization
measure: Percentage of Participants With Severe Acute Graft-versus-host Disease (GVHD)
timeFrame: Day 100 post-transplant
measure: Percentage of Participants With Chronic GVHD
timeFrame: 18 months post-transplant
Other outcomes:
measure: Percentage of Participants With Neutrophil and Platelet Engraftment
timeFrame: Days 7 to 60 post-transplant
measure: Incidence and Percentage of Severe Infection
timeFrame: 18 months post-transplant
measure: Percentage of Participants With Toxicities
timeFrame: Days 1 to 60 post-transplant
measure: Number of Lymphocyte Subsets
timeFrame: Days 28, days 60, 3 months post-transplant, 6 months post-transplant, 12months post-transplant, 18 months post-transplant
Locations:
city: Wuhan
country: China
facility: Wuhan Union Hospital, Tongji Medical college, Huazhong University of Science and Technology
state: Hubei
Study officials:
affiliation: Department of Hematology, Wuhan Union Hospital, Tongji Medical college, Huazhong University of Science and Technology
name: Linghui Xia, Professor
role: STUDY_CHAIR
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