Clinical trial NCT01572181: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hematologic Malignancy
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2012-04-06
Enrollment: 50
Sex: ALL
Minimum age (years): 12
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Transplant-related mortality (TRM)
timeFrame: 12 months
Secondary outcomes:
measure: Incidence of engraftment
timeFrame: Day+42
measure: Evaluation of overall (OS) and disease-free survival (DFS)
timeFrame: 12 months
measure: Cumulative incidence of relapse, death from disease, and non-relapse mortality (NRM)
timeFrame: 12 months
measure: Cumulative incidences and severity of acute and chronic Graft-versus-Host disease
timeFrame: 12 months
measure: Immune Recovery (to be determined in a subgroup of patients)
timeFrame: 12 months
Other outcomes:
Locations:
city: Besançon
country: France
facility: University Hospital
city: Bordeaux
country: France
facility: University Hospital
city: Clermont-Ferrand
country: France
facility: University Hospital
city: Grenoble
country: France
facility: University Hospital
city: Lille
country: France
facility: University Hospital
city: Lyon
country: France
facility: University Hospital
city: Marseille
country: France
facility: University Hospital
city: Montpellier
country: France
facility: University Hospital
city: Nancy
country: France
facility: University Hospital
city: Nantes
country: France
facility: University Hospital
city: Paris
country: France
facility: University Hopsital
city: Paris
country: France
facility: University Hospital
city: Rennes
country: France
facility: University Hospital
city: Rouen
country: France
facility: University Hopsital
city: Strasbourg
country: France
facility: University Hospital
Study officials:
affiliation: Nantes University Hospital
name: Mohamad MOHTY, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rialland F, Grain A, Labopin M, Michel G, Gandemer V, Paillard C, Pochon C, Clement L, Brissot E, Jubert C, Sirvent A, Rohrlich PS, Plantaz D, Dalle JH, Mohty M. Reduced-toxicity myeloablative conditioning regimen using fludarabine and full doses of intravenous busulfan in pediatric patients not eligible for standard myeloablative conditioning regimens: Results of a multicenter prospective phase 2 trial. Bone Marrow Transplant. 2022 Nov;57(11):1698-1703. doi: 10.1038/s41409-022-01769-5. Epub 2022 Aug 26.