Evaluation of 3 Different Doses of IV Busulfan (AAA)

Institut Paoli-Calmettes

Status and phase: Active, not recruiting; Phase 2

Conditions: Myelodysplastic Syndrome; Acute Myeloid Leukemia

Treatments: Drug: BX3; Drug: BX4-Suspended; Drug: BX2

Study type: Interventional

Funder types: Other

Identifiers

NCT01985061

AAA-IPC2011-003

Details and patient eligibility

About

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

Enrollment: 177 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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177 participants in 3 patient groups

BX2

Active Comparator group

Description:

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

Treatment:

Drug: BX2

BX3

Experimental group

Description:

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

Treatment:

Drug: BX3

BX4-Suspended

Active Comparator group

Description:

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

Treatment:

Drug: BX4-Suspended