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)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by Nantes University Hospital
Information provided by (Responsible Party):
Nantes University Hospital Identifier:
First received: February 21, 2012
Last updated: September 18, 2013
Last verified: September 2013
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.

Condition Intervention Phase
Hematologic Malignancy
Drug: Fludarabine IV- Busulfan IV (Busilvex®) - Anti-thymocyte globulines (Thymoglobuline®)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:

Further study details as provided by Nantes University Hospital:

Primary Outcome Measures:
  • Transplant-related mortality (TRM) [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Evaluation of the cumulative incidence of TRM at 12 months after transplantation

Secondary Outcome Measures:
  • Incidence of engraftment [ Time Frame: Day+42 ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Cumulative incidence of relapse, death from disease, and non-relapse mortality (NRM)

  • Cumulative incidences and severity of acute and chronic Graft-versus-Host disease [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Cumulative incidences and severity of acute and chronic Graft-versus-Host disease

  • Immune Recovery (to be determined in a subgroup of patients) [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Immune Recovery parameters: blood counts, bone marrow aspiration with evaluation of morphological response.

Estimated Enrollment: 50
Study Start Date: February 2012
Estimated Study Completion Date: April 2017
Estimated Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Fludarabine IV- Busulfan IV (Busilvex®) - Anti-thymocyte globulines (Thymoglobuline®)
    • IV fludarabine (30 mg/m²/day for 5 days)
    • IV Busulfan (Busilvex 3.2 mg/kg/day for 4 days) (the Busulfan dose is to be adapted to the weight of the child according to the drug label)
    • Anti-thymocyte globulines (Thymogolubuline, 2.5 mg/kg/day for 2 days).

Ages Eligible for Study:   12 Months to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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 applicable)
  • 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 protocol).

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 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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01572181

Contact: Mohamad MOHTY, Professor +33 240 083 206
Contact: Fanny RIALLAND, Doctor +33 240 083 206

University Hospital Recruiting
Besançon, France
Contact: Fabrice LAROSA, Doctor   
Principal Investigator: Fabrice LAROSA, Doctor         
University Hospital Recruiting
Bordeaux, France
Contact: Charlotte JUBERT, Doctor   
Principal Investigator: Charlotte JUBERT, Doctor         
University Hospital Recruiting
Clermont-Ferrand, France
Contact: Justyna KANOLD, Doctor   
Principal Investigator: Catherine PAILLARD, Professor         
University Hospital Recruiting
Grenoble, France
Contact: Dominique PLANTAZ, Professor   
Principal Investigator: Dominique PLANTAZ, Professor         
University Hospital Recruiting
Lille, France
Contact: Bénédicte BRUNO, Doctor   
Principal Investigator: Bénédicte BRUNO, Doctor         
University Hospital Not yet recruiting
Lyon, France
Contact: Yves BERTRAND, Professor   
Principal Investigator: Yves BERTRAND, Professor         
University Hospital Recruiting
Marseille, France
Contact: Gerard MICHEL, Professor   
Principal Investigator: Gerard MICHEL, Professor         
University Hospital Recruiting
Montpellier, France
Contact: Anne SIRVENT, Doctor   
Principal Investigator: Anne SIRVENT, Doctor         
University Hospital Not yet recruiting
Nancy, France
Contact: Laurence CLEMENT, Doctor   
Principal Investigator: Laurence CLEMENT, Doctor         
University Hospital Recruiting
Nantes, France
Contact: Fanny RIALLAND, Doctor   
Principal Investigator: Fanny RIALLAND, Doctor         
University Hopsital Recruiting
Paris, France
Contact: Mohamad MOHTY, Professor,   
Principal Investigator: Mohamad MOHTY, Professor         
University Hospital Recruiting
Paris, France
Contact: Jean-Hugues Dalle, Professor   
Principal Investigator: Jean-Hugues Dalle, Doctor         
University Hospital Recruiting
Rennes, France
Contact: Virginie GANDEMER, Doctor   
Principal Investigator: Virginie GANDEMER, Doctor         
University Hopsital Not yet recruiting
Rouen, France
Contact: Jean-Pierre VANNIER, Professor   
Principal Investigator: Jean-Pierre VANNIER, Professor         
University Hospital Recruiting
Strasbourg, France
Contact: Patrick LUTZ, Professor   
Principal Investigator: Patrick LUTZ, Professor         
Sponsors and Collaborators
Nantes University Hospital
Principal Investigator: Mohamad MOHTY, Professor Nantes University Hospital
  More Information

No publications provided

Responsible Party: Nantes University Hospital Identifier: NCT01572181     History of Changes
Other Study ID Numbers: 11/6-N
Study First Received: February 21, 2012
Last Updated: September 18, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
Fludarabine phosphate
Alkylating Agents
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses processed this record on November 25, 2015