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

Acute Myeloid Leukemia Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05991908
• Other study ID #: MBF-FB4
• Status: Recruiting
• Phase: Phase 3
• Start date: October 19, 2023
• Est. completion date: June 30, 2026

Study information

• Verified date: October 2023
• Source: Shanghai Jiao Tong University School of Medicine
• Contact: chun Wang
• Phone: 13386259777
• Email: wangchunsh[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 222
• Est. completion date: June 30, 2026
• Est. primary completion date: October 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Syndrome

Intervention

Drug:
• Fludarabine, busulfan and melphalan
FLudarabine 150mg/m2 + Busulfan 6.4mg.kg + Mel 140mg/m2
• Fludarabine and Busulfan
FLudarabine 150mg/m2 + Busulfan 12.8mg.kg

Locations

Country	Name	City	State
China	Fujian Medical University Union Hospital	Fuzhou	Fujian
China	920th Hospital PLA	Kunming
China	First Affiliated Hospital of Nanjin Medical Unviersity	Nanjin	Jiangsu
China	923th Hospital PLA	Nanning	Guangxi
China	Ruijin Hospital	Shanghai	Shanghai
China	Shanghai No 6 Hospital	Shanghai
China	Shanghai No10 Hospital	Shanghai	Shanghai
China	First Affiliatied Hospital of Soochow University	Suzhou	Jiang Su
China	Zhongshan Hospital, Xianmen University	Xiamen	Fujian

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Jiao Tong University School of Medicine

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	disease-free survival	event defined as relapse and death of any causes	2 year
Secondary	overall survival	event defined as death of any causes	2 year
Secondary	incidence of relapse	event defined as disease relapse (bone marrow or extra medullary)	2 year
Secondary	non relapse mortality	event defined as death without disease relapse	day 100
Secondary	non relapse mortality	event defined as death without disease relapse	2 year