Study of a Reduced-toxicity Myeloablative Conditioning Regimen Using Fludarabine and Full Doses of Intravenous Busulfan in Pediatric Patients Not Eligible for Standard Myeloablative Conditioning Regimens
- Conditions
- Hematologic Malignancy
- Interventions
- Registration Number
- NCT01572181
- Lead Sponsor
- Nantes University Hospital
- Brief Summary
The purpose of this study is to assess transplant-related mortality (TRM) at one year after allogeneic hematopoietic stem cell transplantation (allo-HSCT) prepared by a "reduced toxicity myeloablative" conditioning regimen in young patients (children and adolescents) with hematologic malignancies.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 50
Not provided
- Patient has been administered any other systemic chemotherapeutic drug (including Gemtuzumab) within 21 days prior to trial enrollment and start of the conditioning regimen. Hydroxyurea is permitted if indicated to control induction refractory disease, and IT chemotherapy is allowed if indicated as maintenance treatment for previously diagnosed leptomeningeal disease, that has been in remission for at least 3 months prior to enrollment on this study.
- Active infection. Protocol PI will be final arbiter if there is uncertainty regarding whether a previous infection is resolved.
- Children and adolescents who are not older than 12 months and under 25 years
- A donor who is HLA mismatched at the level of more than one locus.
- Poor performance status (Lansky < 50%)
- Life expectancy is severely limited by concomitant illness and expected to be <12 weeks.
- Left ventricular ejection fraction < 30%. Uncontrolled arrhythmias or symptomatic cardiac disease.
- Symptomatic pulmonary disease. FEV1, FVC and DLCO <30% of expected corrected for hemoglobin.
- Creatinine clearance less than 30 mL/m per 1.73 m2 or requiring dialysis
- Evidence of chronic active hepatitis or cirrhosis. If positive hepatitis serology, discuss with Study Chairman and consider liver biopsy.
- Effusion or ascites >1L prior to drainage.
- HIV-positive.
- Female pregnancy
- Absence of effective contraception among boys and girls of childbearing potential (that contraception should be continued until 6 months after stopping treatment)
- Breastfeeding
- Patient's legal representative, parent(s) or guardian not able to sign informed consent.
- children's refusal
- Hypersensitivity to rabbit proteins, to the active substance or to any of the excipients of experimental products
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Drugs Fludarabine IV- Busulfan IV (Busilvex®) - Anti-thymocyte globulines (Thymoglobuline®) Fludarabine IV- Busulfan IV (Busilvex®) - Anti-thymocyte globulines (Thymoglobuline®)
- Primary Outcome Measures
Name Time Method Transplant-related mortality (TRM) 12 months Evaluation of the cumulative incidence of TRM at 12 months after transplantation
- Secondary Outcome Measures
Name Time Method Incidence of engraftment Day+42 Incidence of engraftment defined as the first day of neutrophil (\>500/μl for 3 consecutive days). Engraftment failure is defined as neutrophil \<500/μl at day+42 after allo-SCT.
Evaluation of overall (OS) and disease-free survival (DFS) 12 months Evaluation of overall (OS) and disease-free survival (DFS) at 1 year after transplantation
Cumulative incidence of relapse, death from disease, and non-relapse mortality (NRM) 12 months Cumulative incidence of relapse, death from disease, and non-relapse mortality (NRM)
Cumulative incidences and severity of acute and chronic Graft-versus-Host disease 12 months Cumulative incidences and severity of acute and chronic Graft-versus-Host disease
Immune Recovery (to be determined in a subgroup of patients) 12 months Immune Recovery parameters: blood counts, bone marrow aspiration with evaluation of morphological response.
Trial Locations
- Locations (2)
University Hospital
🇫🇷Strasbourg, France
University Hopsital
🇫🇷Rouen, France