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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 has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01572181
First Posted: April 6, 2012
Last Update Posted: November 27, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Nantes University Hospital
  Purpose
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: Intervention Model: Single Group Assignment
Masking: None (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 ]
    Evaluation of the cumulative incidence of TRM at 12 months after transplantation


Secondary Outcome Measures:
  • Incidence of engraftment [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 12 months ]
    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 ]
    Immune Recovery parameters: blood counts, bone marrow aspiration with evaluation of morphological response.


Enrollment: 50
Actual Study Start Date: April 2012
Study Completion Date: October 24, 2017
Primary Completion Date: October 24, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Drugs
Fludarabine IV- Busulfan IV (Busilvex®) - Anti-thymocyte globulines (Thymoglobuline®)
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).

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   12 Months to 25 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01572181


Locations
France
University Hospital
Besançon, France
University Hospital
Bordeaux, France
University Hospital
Clermont-Ferrand, France
University Hospital
Grenoble, France
University Hospital
Lille, France
University Hospital
Lyon, France
University Hospital
Marseille, France
University Hospital
Montpellier, France
University Hospital
Nancy, France
University Hospital
Nantes, France
University Hopsital
Paris, France
University Hospital
Paris, France
University Hospital
Rennes, France
University Hopsital
Rouen, France
University Hospital
Strasbourg, France
Sponsors and Collaborators
Nantes University Hospital
Investigators
Principal Investigator: Mohamad MOHTY, Professor Nantes University Hospital
  More Information

Responsible Party: Nantes University Hospital
ClinicalTrials.gov Identifier: NCT01572181     History of Changes
Other Study ID Numbers: BRD/11/06-N
First Submitted: February 21, 2012
First Posted: April 6, 2012
Last Update Posted: November 27, 2017
Last Verified: November 2017

Additional relevant MeSH terms:
Fludarabine
Fludarabine phosphate
Busulfan
Thymoglobulin
Vidarabine
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antiviral Agents
Anti-Infective Agents
Alkylating Agents
Antineoplastic Agents, Alkylating
Myeloablative Agonists