Conditioning Regimen of Melphalan-busulfan and Fludarabine: a Randomized Study of Different Dose of Melphalan

Conditioning Regimen of Melphalan-busulfan and Fludarabine: a Randomize Study Comparing 100mg/m2 to 140mg/m2 Melphalan for Adult Patients With Acute Myeloid Leukemia or Myelodysplasia Syndrome.

Conditioning regimen with melphalan-busulfan and fludarabine (MBF) achieved low relapse rate in patients with acute myeloid leukemia (AML) and myelodysplasia syndrome (MDS). In our previous retrospective study, we demonstrated that melphalan dose at 100 or 140mg/m2 had similar incidence of relapse but it might had lower toxicities. In this prospective randomize study, we aim to compare the transplantation outcome in adult patients with AML/MDS receiving either MBF with 100 or 140 mg/m2 melphalan.

Study Overview

• Status: Recruiting
• Conditions: Survivorship; Toxicities
• Intervention / Treatment: Drug: melphalan

Detailed Description

Intensity of conditioning regimen plays a important role in allogeneic stem cell transplantation (allo-HSCT) for patents with AML and MDS. IN our previous prospective study, we demonstrated that condoning regimen of dual alkylating agents with melphalan-busulfan and fludarabine (MBF) achieved a very low relapse rate (~6%) in patients with acute myeloid leukemia (AML) and myelodysplasia syndrome (MDS). In that study, adult patients received melphalan 140mg/m2 while patients >=60 or with high transplantation risk in terms of HCT-CI received reduced dose of melphalan (100mg/m2). Overall, it was shown that 100 or 140mg/m2 melphalan had similar incidence of relapse while the 100mg/m2 melphalan presented lower incidence of toxicities.In this prospective randomize study, we aim to compare the transplantation toxicities and outcomes in young adults (18~55) with AML/MDS receiving either 100 or 140 mg/m2 melphalan as conditioning regimen.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Chun Wang; Phone Number: 86-13386259777; Email: Wangchunsh@mefmail.com.cn

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Recruiting
      • Rui Jin Hospital
      • Contact: Jiong Hu; Phone Number: 86-13764313546; Email: hj10709@rjh.com.cn
    • Shanghai, Shanghai, China
      • Not yet recruiting
      • Zhaxin Hospital, Go Broad Health Care
      • Contact: Chun Wang; Phone Number: 86-13386259777; Email: wangchunsh@medmail.com.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with AML in first remission
• Patients with MDS with bone marrow blast >5% but remain less than 20% before transplantation
• Donor available: HLA matched sibling donor, 9~10/10 matched unrelated donor or haplo-identical donor
• Inform consent provided

Exclusion Criteria:

• Patients with active infection (bacteria, fungal or viral)
• Patients with abnormal liver, renal and cardiac function

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MBF100; Patients receive condoning regimen with melphalan (100mg/m2) with busulfan and fludarabine.	Drug: melphalan; conditioning regimen with melphalan, busulfan and fludarabine; Other Names: MBF
Active Comparator: MBF140; Patients receive condoning regimen with melphalan (140mg/m2) with busulfan and fludarabine.	Drug: melphalan; conditioning regimen with melphalan, busulfan and fludarabine; Other Names: MBF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicities	Toxicities with grade III or over	up to 100 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse	Documentation of bone marrow blasts >5% or extra medullary disease	2 years
Non-relapse mortality	Death without documentation of AML and MDS disease	100 days
Non-relapse mortality	Death without documentation of AML and MDS disease	2 years
disease-free survival	event defined as documentation of AML and MDS relapse or death of any causes	2 years
overall survival	event defined as death of any causes	2 years

Collaborators and Investigators

• Sponsor: Shanghai Jiao Tong University School of Medicine
• Collaborators: Shanghai Clinical Research Center
• Investigators: Study Director: chun Wang, Go Broad Health Care

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: August 12, 2023
• First Submitted That Met QC Criteria: February 14, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 14, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: melphalan, AML, MDS, allogeneic stem cell transplantation
• Additional Relevant MeSH Terms: Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Melphalan
• Other Study ID Numbers: MBF-RJH-2023

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No