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 (FB4-PEDIA)

Nantes University Hospital (NUH)

Status and phase

Completed

Phase 2

Conditions

Hematologic Malignancy

Treatments

Drug: Fludarabine IV- Busulfan IV (Busilvex®) - Anti-thymocyte globulines (Thymoglobuline®)

Study type

Interventional

Funder types

Other

Identifiers

NCT01572181

BRD/11/06-N

Details and patient eligibility

About

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.

Enrollment

50 patients

Sex

All

Ages

12 months to 25 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

Children and adolescents aged over 12 months and under 25 years
Availability of an HLA identical family donor or an HLA-matched unrelated donor (10/10 or 9/10 if the mismatch level is at HLACw for an unrelated donor) or availability of an HLA matched cord blood (5/6 or 6/6)
Informed consent signed by patients (18-25 years) and patient's legal representative, parent(s) or guardian (cf p13)
Diagnosis of a hematologic malignancy which is a candidate for allo-HSCT, but not eligible for standard or conventional myeloablative conditioning regimens because of high risk for toxicity.
Are considered as criteria of non-eligibility for standard or conventional myeloablative conditioning:
- a history of autologous or allogeneic stem cell transplantation
- comorbidities or medical history predictive of a prohibitive rate of TRM and toxicity with the use of standard high dose chemotherapy and / or radiotherapy.

Exclusion Criteria:

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