Clinical trial NCT01985061: Evaluation of 3 Different Doses of IV Busulfan
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Myelodysplastic Syndrome
Acute Myeloid Leukemia
Keywords: Myelodysplasic syndrome
Acute Myeloid leukemia
Lead sponsor: Institut Paoli-Calmettes
Sponsor class: OTHER
First posted: 2013-11-15
Enrollment: 177
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Time to progression or death
timeFrame: up to 2 years
Secondary outcomes:
measure: Time to neutrophil>0.5G/l and platelets>50G/l
timeFrame: up to 2 months
measure: Graft versus host disease
timeFrame: up to 2 years
measure: relapse
timeFrame: up to 2 years
measure: Occurrence of grade 3-4 adverse events according the CTC-AE v4.0 scale
timeFrame: up to 6 months
Other outcomes:
Locations:
city: Marseille
country: France
facility: Institut Paoli Calmettes
Study officials:
affiliation: Institut Paoli-Calmettes
name: Didier BLAISE, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.