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

Shanghai Jiao Tong University School of Medicine

Status and phase: Enrolling; Phase 3

Conditions: Myelodysplastic Syndromes; Acute Myeloid Leukemia

Treatments: Drug: Fludarabine, busulfan and melphalan; Drug: Fludarabine and Busulfan

Study type: Interventional

Funder types: Other

Identifiers

NCT05991908

MBF-FB4

Details and patient eligibility

About

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.

Full 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.

Enrollment: 222 estimated patients

Sex: All

Ages: 16 to 55 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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222 participants in 2 patient groups

Flu-Bu2-Mel140

Experimental group

Description:

Patients receive fludarabine, busulfan and melphalan as conditioning regimen

Treatment:

Drug: Fludarabine, busulfan and melphalan

Flu-Bu4

Active Comparator group

Description:

Patients receive fludarabine and busulfan as conditioning regimen

Treatment:

Drug: Fludarabine and Busulfan