Clinical trial NCT05991908: Randomized Study of Conditioning of Fludarabine Combined With Single or Dual Alkylating Agents in Myeloid Malignancies
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Acute Myeloid Leukemia
Myelodysplastic Syndromes
Keywords: conditioning regimen, melphalan, busulfan, fludarabine
Lead sponsor: Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
First posted: 2023-08-15
Enrollment: 222
Sex: ALL
Minimum age (years): 16
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: study group with fludarabine, busulfan and melphalan regimen versus control group with fludarabine and busulfan
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: disease-free survival
timeFrame: 2 year
Secondary outcomes:
measure: overall survival
timeFrame: 2 year
measure: incidence of relapse
timeFrame: 2 year
measure: non relapse mortality
timeFrame: day 100
measure: non relapse mortality
timeFrame: 2 year
Other outcomes:
Locations:
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Xiamen
country: China
facility: Zhongshan Hospital, Xianmen University
state: Fujian
city: Nanning
country: China
facility: 923th Hospital PLA
state: Guangxi
city: Suzhou
country: China
facility: First Affiliatied Hospital of Soochow University
state: Jiang Su
city: Nanjin
country: China
facility: First Affiliated Hospital of Nanjin Medical Unviersity
state: Jiangsu
city: Shanghai
country: China
facility: Ruijin Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai No10 Hospital
state: Shanghai
city: Kunming
country: China
facility: 920th Hospital PLA
city: Shanghai
country: China
facility: Shanghai No 6 Hospital
Study officials:
affiliation: Go Broad Health Center, Zhaxin Hospital
name: Chun Wang
role: PRINCIPAL_INVESTIGATOR
References: