Randomized Study of Conditioning of Fludarabine Combined With Single or Dual Alkylating Agents in Myeloid Malignancies

Sponsor

Shanghai Jiao Tong University School of Medicine (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT05991908

Collaborator

(none)

222

Enrollment

Locations

Arms

Anticipated Duration (Months)

24.7

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Fludarabine and busulfan becomes standard conditioning regimen for adult patients with acute myeloid leukemia (AML) or myelodysplasia syndrome (MDS). The overall relapse rate is 15~20%. More recently, the investigators demonstrated that conditioning regimen with dual alkylating agents consistent of fludarabine, busulfan and melphalan achieved a low incidence of relapse (<10%). This multiple-center randomize study is aim to compare the transplantation outcome in adult patients with AML/MDS undergoing allo-HSCT with conditioning regimen of Flu-Bu4 vs. FLu-Bu-Mel.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia Myelodysplastic Syndromes	Drug: Fludarabine, busulfan and melphalan Drug: Fludarabine and Busulfan	Phase 3

Detailed Description

Fludarabine and busulfan was considered as myeloablative but reduced toxicity regimen and became as the mainstay of conditioning regimen for adult patients with acute myeloid leukemia (AML) or myelodysplasia syndrome (MDS). The disease relapse remained as major cause of treatment failure. In general, the cumulated incidence of relapse (CIR) is about 15~20% dependent on the risk of patients undergoing allogeneic stem cell transplantation (allo-HSCT). Conditioning regimen with dual alkylating agents such as fludarabine, busulfan and thiotepa (TBF) showed decreased risk of relapse in myeloid malignancies. More recently, the investigators demonstrated that conditioning regimen with dual alkylating agents consistent of fludarabine, busulfan and melphalan could achieve a low incidence of relapse (2 year CIR <10%). In this multiple-center randomize study, the aim is to compare the transplantation outcome in adult patients with AML/MDS undergoing allo-HSCT with conditioning regimen of Flu-Bu vs. Flu-Bu-Mel.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

222 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

study group with fludarabine, busulfan and melphalan regimen versus control group with fludarabine and busulfanstudy group with fludarabine, busulfan and melphalan regimen versus control group with fludarabine and busulfan

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Multiple-center Randomized Study to Compare Fludarabine and Busulfan Versus Fludarabine, Busulfan and Melphalan in Adult Patients With Acute Myeloid Leukemia (AML) and Myelodysplasia Syndrome (MDS)

Actual Study Start Date :

Aug 1, 2023

Anticipated Primary Completion Date :

Jun 30, 2025

Anticipated Study Completion Date :

Jun 30, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Flu-Bu2-Mel140 Patients receive fludarabine, busulfan and melphalan as conditioning regimen	Drug: Fludarabine, busulfan and melphalan FLudarabine 150mg/m2 + Busulfan 6.4mg.kg + Mel 140mg/m2
Active Comparator: Flu-Bu4 Patients receive fludarabine and busulfan as conditioning regimen	Drug: Fludarabine and Busulfan FLudarabine 150mg/m2 + Busulfan 12.8mg.kg

Arm

Intervention/Treatment

Experimental: Flu-Bu2-Mel140

Patients receive fludarabine, busulfan and melphalan as conditioning regimen

Drug: Fludarabine, busulfan and melphalan

FLudarabine 150mg/m2 + Busulfan 6.4mg.kg + Mel 140mg/m2

Active Comparator: Flu-Bu4

Patients receive fludarabine and busulfan as conditioning regimen

Drug: Fludarabine and Busulfan

FLudarabine 150mg/m2 + Busulfan 12.8mg.kg

Outcome Measures

Primary Outcome Measures

disease-free survival [2 year]
event defined as relapse and death of any causes

Secondary Outcome Measures

overall survival [2 year]
event defined as death of any causes
incidence of relapse [2 year]
event defined as disease relapse (bone marrow or extra medullary)
non relapse mortality [day 100]
event defined as death without disease relapse
non relapse mortality [2 year]
event defined as death without disease relapse

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

acute myeloid leukemia (acute promyelocytic leukemia excluded) in 1st complete remission
myelodysplasia syndrome with bone marrow blast >5% and remaining less than 20% at transplantation
patients with HLA matched sibling donor, 9-10 matched unrelated donor or haplo-identical related donors
inform consent provided

Exclusion Criteria:

AML patients with active CNS or extramedullary diseases
patients with active viral, bacterial or fungal infection
patients with hepatitis B virus >1X103 copy/ml
patients with abnormal liver function, renal function, respiratory or cardiac dysfunction
patients with uncontrolled mental disorders
patients with HIV

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fujian Medical University Union Hospital	Fuzhou	Fujian	China	350001
2	Zhongshan Hospital, Xianmen University	Xiamen	Fujian	China	361004
3	923th Hospital PLA	Nanning	Guangxi	China	530021
4	First Affiliatied Hospital of Soochow University	Suzhou	Jiang Su	China	215006
5	First Affiliated Hospital of Nanjin Medical Unviersity	Nanjin	Jiangsu	China	210029
6	Ruijin Hospital	Shanghai	Shanghai	China	200025
7	Shanghai No10 Hospital	Shanghai	Shanghai	China
8	920th Hospital PLA	Kunming		China	650000
9	Shanghai No 6 Hospital	Shanghai		China