Phase 2 Study of a Reduced-toxicity Myeloablative Conditionning Regimen Using Fludarabine and Full Doses of iv Busulfan in Pediatric Patients Not Eligible for Standard Myeloablative Conditioning Regimens
- Children and adolescents aged over 12 months and under 18 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 the level of HLACw)
- Informed consent signed by legal representative and confirmed by children (if
- 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 as judged by the referring physician (details provided in the full
- 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 18 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
- Left ventricular ejection fraction < 30%. Uncontrolled arrhythmias or symptomatic
- Symptomatic pulmonary disease. FEV1, FVC and DLCO <30% of expected corrected for
- 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.
- Female pregnancy
- Absence of effective contraception among boys and girls of childbearing potential
(that contraception should be continued until 6 months after stopping treatment)
- Patient's legal representative, parent(s) or guardian not able to sign informed
- children's refusal
- Hypersensitivity to rabbit proteins, to the active substance or to any of the
excipients of experimental products