Reduced Intensity Conditioning Regimens for Acute Myeloid Leukemia and Myelodysplastic Syndrome
- Conditions
- Myelodysplastic Syndrome(MDS)Acute Myeloid Leukemia, AdultAllogeneic Hematopoietic Stem Cell Transplantation
- Interventions
- Registration Number
- NCT05674539
- Lead Sponsor
- Wuhan Union Hospital, China
- 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.
Recruitment & Eligibility
- Status
- ENROLLING_BY_INVITATION
- Sex
- All
- Target Recruitment
- 200
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description fludarabine and melphalan 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) fludarabine and busulfan 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)
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) 18 months post-randomization Survival without relapse or progression of the primary disease. Kaplan-Meier (KM) method was used to estimate median PFS.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Chronic GVHD 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)
Non-Relapse Mortality (NRM) 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.
Percentage of Participants With Severe Acute Graft-versus-host Disease (GVHD) 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 4Overall Survival (OS) 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
Disease Relapse 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.
Trial Locations
- Locations (1)
Wuhan Union Hospital, Tongji Medical college, Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China