Reduced Intensity Conditioning Regimens for Acute Myeloid Leukemia and Myelodysplastic Syndrome

Sponsor

Wuhan Union Hospital, China (Other)

Overall Status

Recruiting

CT.gov ID

NCT05674539

Collaborator

(none)

200

Enrollment

Location

Arms

30.1

Anticipated Duration (Months)

6.7

Patients Per Site Per Month

Study Details

Study Description

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)

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia, Adult Myelodysplastic Syndrome(MDS) Allogeneic Hematopoietic Stem Cell Transplantation	Drug: Fludarabine and Busulfan Drug: Fludarabine and Melphalan	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

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

Masking:

None (Open Label)

Primary Purpose:

Treatment

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, Single-Center, Phase III Study

Anticipated Study Start Date :

Dec 28, 2022

Anticipated Primary Completion Date :

Jan 15, 2025

Anticipated Study Completion Date :

Jun 30, 2025

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

Overall 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
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.
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.
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 4
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)

Other Outcome Measures

Percentage of Participants With Neutrophil and Platelet Engraftment [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.
Incidence and Percentage of Severe Infection [18 months post-transplant]
List the type, number, and severity of infection events
Percentage of Participants With Toxicities [Days 1 to 60 post-transplant]
The severity of oral ulcer or diarrhea in the early stage after transplantation, clinically significant abnormal laboratory findings.
Number of Lymphocyte Subsets [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Wuhan Union Hospital, Tongji Medical college, Huazhong University of Science and Technology	Wuhan	Hubei	China	430000

Sponsors and Collaborators

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