Evaluation of 3 Different Doses of IV Busulfan

NCT01985061 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: AAA-IPC2011-003
• Study Type: interventional
• Target: 177
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Myelodysplastic Syndrome; Acute Myeloid Leukemia

Keywords

Myelodysplasic syndrome; Acute Myeloid leukemia

Outcome Measures

Primary Outcomes (1)

• Time to progression or death

  2-year progression free survival rates

  up to 2 years

Secondary Outcomes (4)

• Time to neutrophil>0.5G/l and platelets>50G/l

  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

  up to 6 months

Study Arms (3)

BX2

ACTIVE COMPARATOR

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

BX3

EXPERIMENTAL

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

BX4-Suspended

ACTIVE COMPARATOR

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

Interventions

BX2 DRUG

Also known as: Busulfan Intravenous 2 days at 3.2 mg/kg/d

BX2

BX3 DRUG

Also known as: Busulfan Intravenous 3 days

BX3

BX4-Suspended DRUG

Suspended

Also known as: Busulfan intravenous 4 days

BX4-Suspended

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with poor prognosis myeloid malignancies:
• Myelodysplastic syndrome,
• Acute Myeloid Leukemia (AML) beyond Complete Response (CR1),
• CR1 AML with poor risk cytogenetics
• 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.
• Availability of a HLA identical sibling or matched unrelated donor (10/10)
• Affiliation to social security
• Written Informed Consent

You may not qualify if:

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

Sponsors & Collaborators

• Institut Paoli-Calmettes: lead

Study Sites (1)

Institut Paoli Calmettes

Marseille, 13009, France

Location

Related Publications (1)

• 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.

  PMID: 26885686 DERIVED

Related Links

• official web site of the sponsor

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Didier BLAISE, MD PhD

  Institut Paoli-Calmettes

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2013
• First Posted: November 15, 2013
• Study Start: December 1, 2013
• Primary Completion (Estimated): July 7, 2026
• Study Completion (Estimated): July 7, 2026
• Last Updated: June 15, 2025

Record last verified: 2025-06

Locations

FR (1)