Evaluation of 3 Different Doses of IV Busulfan (AAA)

Prospective and Multicentre Evaluation of 3 Different Doses of IV Busulfan Associated With Fludarabine and Thymoglobuline in the Conditioning of Allogeneic Stem Cell Transplantation (SCT) From a Matched Related or Unrelated Donor in Patients With Poor Prognosis Myeloid Malignancies

Albeit the safety of the stem cell transplantation procedure has been greatly improved, further refining the intensity of the conditioning is an important issue to explore, especially in patients with poor prognosis, the goal being to maintain the very favorable safety profile and improve the disease control. This is the goal our prospective trial; we aim to prospectively evaluate in a prospective multicenter trial the efficacy of different conditioning regimens in patients with high-risk myeloid malignancies.

The study is a phase II trial randomizing patients between a prospective active control arm (BX2) and two experimental arms (BX3 and BX4). A standard group was kept in this clinical trial in order to avoid the limitations induced by the comparison with historical controls in the context of continuously improving practice. Each experimental arm will be conducted in parallel according to a standard phase II trial design.

In addition, this trial will associate four ancillary studies to the main clinical objective: 1/ a prospective assessment of the quality of life of the patients over a period of 2 years 2/ an analysis of the cost effectiveness of the procedure, assessed over a period of 2 years 3/ an observational busulfan pharmacokinetic study 4/ a busulfan pharmacogenomic study

Study Overview

• Status: Active, not recruiting
• Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndrome
• Intervention / Treatment: Drug: BX2; Drug: BX3; Drug: BX4-Suspended

• Study Type: Interventional
• Enrollment (Estimated): 177
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Marseille, France, 13009
    • Institut Paoli Calmettes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients with poor prognosis myeloid malignancies:

   • Myelodysplastic syndrome,
   • Acute Myeloid Leukemia (AML) beyond Complete Response (CR1),
   • CR1 AML with poor risk cytogenetics
2. Adult patients: aged ≥ 55 years up to 65 or < 55 years not eligible for myeloablative conditioning regimen based on Total Body Irradiation (TBI) or double alkylating agent combinations.
3. Availability of a HLA identical sibling or matched unrelated donor (10/10)
4. Affiliation to social security
5. Written Informed Consent

Exclusion Criteria:

1. History of previous Allo-Hematological Stem Cell Transplantation (HSCT)
2. HIV positivity
3. Signs of chronic active hepatitis B and/or C
4. Evolutive psychiatric disease
5. Concomitant neoplastic disease
6. Pregnant or lactating woman or without contraception (for child bearing potential wom-en)
7. Usual contra-indications for Allo-HSCT

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: BX2; Fludarabine (Fludara®): 30 mg/m2 on D-6, D-5, D-4, D-3 and D-2 Busulfan IV (Busilvex®) : 3.2 mg/kg/d on D-4 and D-3 Thymoglobuline®: 2.5 mg/kg/d on D-3 and D-2	Drug: BX2; Other Names: Busulfan Intravenous 2 days at 3.2 mg/kg/d
Experimental: BX3; Fludarabine (Fludara®): 30 mg/m² on D-6, D-5, D-4, D-3 and D-2 Busulfan IV (Busilvex®) : 3.2 mg/kg/d on D-5, D-4 and D-3 Thymoglobuline® : 2.5 mg/kg/d on D-3 and D-2	Drug: BX3; Other Names: Busulfan Intravenous 3 days
Active Comparator: BX4-Suspended; Fludarabine (Fludara®): 30 mg/m²on D-6, D-5, D-4, D-3 and D-2 Busulfan IV (Busilvex®) : 3.2 mg/kg/d on D-6, D-5, D-4 and D-3 Thymoglobuline® : 2.5 mg/kg/d on D-3 and D-2	Drug: BX4-Suspended; Suspended; Other Names: Busulfan intravenous 4 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to progression or death	2-year progression free survival rates	up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to neutrophil>0.5G/l and platelets>50G/l	hematologic recovery	up to 2 months
Graft versus host disease		up to 2 years
relapse		up to 2 years
Occurrence of grade 3-4 adverse events according the CTC-AE v4.0 scale	safety	up to 6 months

Collaborators and Investigators

• Sponsor: Institut Paoli-Calmettes
• Investigators: Principal Investigator: Didier BLAISE, MD PhD, Institut Paoli-Calmettes

Publications and helpful links

General Publications

• Wanquet A, Crocchiolo R, Furst S, Granata A, Faucher C, Devillier R, Harbi S, Lemarie C, Calmels B, Vey N, Weiller PJ, Chabannon C, Castagna L, Blaise D, El-Cheikh J. The efficacy and safety of a new reduced-toxicity conditioning with 4 days of once-daily 100 mg/m(2) intravenous busulfan associated with fludarabine and antithymocyte globulins prior to allogeneic stem cell transplantation in patients with high-risk myelodysplastic syndrome or acute leukemia. Leuk Lymphoma. 2016 Oct;57(10):2315-20. doi: 10.3109/10428194.2016.1146948. Epub 2016 Feb 17.

Helpful Links

• official web site of the sponsor

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2013
• Primary Completion (Estimated): July 7, 2026
• Study Completion (Estimated): July 7, 2026

Study Registration Dates

• First Submitted: October 31, 2013
• First Submitted That Met QC Criteria: November 7, 2013
• First Posted (Estimated): November 15, 2013

Study Record Updates

• Last Update Posted (Actual): June 15, 2025
• Last Update Submitted That Met QC Criteria: June 13, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Acute Myeloid leukemia; Myelodysplasic syndrome
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Bone Marrow Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Busulfan
• Other Study ID Numbers: AAA-IPC2011-003