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

Phase 3
Recruiting
Conditions
Acute Myeloid Leukemia
Myelodysplastic Syndromes
Interventions
Drug: Fludarabine, busulfan and melphalan
Registration Number
NCT05991908
Lead Sponsor
Shanghai Jiao Tong University School of Medicine
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.

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
222
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Flu-Bu2-Mel140Fludarabine, busulfan and melphalanPatients receive fludarabine, busulfan and melphalan as conditioning regimen
Flu-Bu4Fludarabine and BusulfanPatients receive fludarabine and busulfan as conditioning regimen
Primary Outcome Measures
NameTimeMethod
disease-free survival2 year

event defined as relapse and death of any causes

Secondary Outcome Measures
NameTimeMethod
overall survival2 year

event defined as death of any causes

incidence of relapse2 year

event defined as disease relapse (bone marrow or extra medullary)

non relapse mortality2 year

event defined as death without disease relapse

Trial Locations

Locations (9)

Zhongshan Hospital, Xianmen University

🇨🇳

Xiamen, Fujian, China

Fujian Medical University Union Hospital

🇨🇳

Fuzhou, Fujian, China

First Affiliated Hospital of Nanjin Medical Unviersity

🇨🇳

Nanjin, Jiangsu, China

923th Hospital PLA

🇨🇳

Nanning, Guangxi, China

First Affiliatied Hospital of Soochow University

🇨🇳

Suzhou, Jiang Su, China

Ruijin Hospital

🇨🇳

Shanghai, Shanghai, China

Shanghai No10 Hospital

🇨🇳

Shanghai, Shanghai, China

920th Hospital PLA

🇨🇳

Kunming, China

Shanghai No 6 Hospital

🇨🇳

Shanghai, China

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