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Trial record 1 of 1 for:    NCT02349906
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Treosulfan-based Versus Busulfan-based Conditioning in Paediatric Patients With Non-malignant Diseases

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ClinicalTrials.gov Identifier: NCT02349906
Recruitment Status : Recruiting
First Posted : January 29, 2015
Last Update Posted : August 16, 2018
Sponsor:
Collaborators:
Celerion
Therametrics
Syneos Health
Information provided by (Responsible Party):
medac GmbH

Tracking Information
First Submitted Date  ICMJE January 26, 2015
First Posted Date  ICMJE January 29, 2015
Last Update Posted Date August 16, 2018
Study Start Date  ICMJE April 2015
Estimated Primary Completion Date December 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 26, 2015)
Comparative evaluation of freedom from transplant (treatment)-related mortality (TRM), defined as death from any transplant-related cause from the day of first administration of study medication (day -7) until day +100 after HSCT. [ Time Frame: day -7 to day +100 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02349906 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Treosulfan-based Versus Busulfan-based Conditioning in Paediatric Patients With Non-malignant Diseases
Official Title  ICMJE Clinical Phase II Trial to Compare Treosulfan-based Conditioning Therapy With Busulfan-based Conditioning Prior to Allogeneic Haematopoietic Stem Cell Transplantation (HSCT) in Paediatric Patients With Non-malignant Diseases
Brief Summary The aim of the trial is to describe the safety and efficacy of intravenous (i.v.) Treosulfan compared to the conventional (myeloablative) dose of i.v. Busulfan, each administered as part of a standardised Fludarabine-containing conditioning regimen and to contribute to a PK model which permits - in conjunction with data comparing Treosulfan and Busulfan in adults with malignant diseases - to extend the use of Treosulfan in the paediatric population by extrapolating efficacy.
Detailed Description

The prospective clinical phase II protocol MC-FludT.16/NM is to be conducted to verify safety and efficacy of Treosulfan-based conditioning compared to Busulfan-based conditioning in paediatric patients. Based on the given clinical experience with either Treosulfan-based or Busulfan-based conditioning in combination with Fludarabine no increased risk for graft failure is expected in paediatric patients. A potential benefit for study patients is expected with respect to a probably low non-haematological toxicity of treatment compared to myeloablative TBI-based conditioning or high-dose Busulfan-based conditioning in combination with Cyclophosphamide.

However, the allogeneic HSCT procedure itself potentially involves serious risks with regard to severe or life-threatening conditions like graft versus host disease (GvHD) and/or infectious complications as well as graft failure.

In summary, the primary goal of this study is to evaluate the Treosulfan-based myeloablative conditioning regimen as an alternative in children and to contribute to the current PK model for Treosulfan to be able to finally give age (or body surface area [BSA]) dependent dose recommendations. The treatment regimens given in the protocol MC-FludT.16/NM are based on sufficient clinical safety and efficacy data. Considering the vital indication for allogeneic HSCT of the selected patient population, the risk-benefit assessment seems to be in favour of the study conduct.

Moreover, planned interim analyses will ensure the early identification of unexpected risks. Therefore, the conduct of the protocol MC-FludT.16/NM is considered reasonably justified.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Primary Immunodeficiencies
  • Inborn Errors of Metabolism
  • Haemoglobinopathies
  • Bone Marrow Failure Syndromes
Intervention  ICMJE
  • Drug: Treosulfan
  • Drug: Busilvex
Study Arms  ICMJE
  • Experimental: Treosulfan
    One Treosulfan dose per day (10, 12 or 14 g/m2/day, based on body surface area) administered i.v. on three consecutive days (-6, -5 and -4); given over 2 hours as part of background conditioning regimen prior to allogeneic stem cell transplantation.
    Intervention: Drug: Treosulfan
  • Active Comparator: Busulfan
    Total daily Busilvex dose (3.2 to 4.8 mg/kg/day, based on body weight) according to authorised dosage for children and adolescents administered i.v. as part of the background conditioning regimen on four consecutive days (days -7, -6, -5 and -4); given in 1, 2, or 4 portions per day according to the respective hospital's standard.
    Intervention: Drug: Busilvex
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 26, 2015)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2019
Estimated Primary Completion Date December 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Non-malignant disease indicated for first myeloablative allogeneic HSCT, including inborn errors of metabolism, primary immunodeficiencies, haemoglobinopathies and bone marrow failure syndromes.
  2. First allogeneic HSCT.
  3. Available matched sibling donor (MSD), matched family donor (MFD) or matched unrelated donor (MUD). For bone marrow (BM) and peripheral blood (PB) match is defined as at least 9/10 allele matches after four digit typing in human leucocyte antigen (HLA)-A, -B, -C, -DRB1 and DQB1 antigens. For umbilical cord blood (UCB) match is defined as at least 5/6 matches after two digit typing in HLA-A and -B and four digit typing in DRB1 antigens.

Exclusion Criteria:

  1. Second or later HSCT.
  2. HSCT from mismatched donor (less than 9/10 BM/peripheral blood stem cells (PBSC) or less than 5/6 matched cord donor).
  3. Preterm newborn infants (<37 weeks gestational age) and term newborn infants aged 0 - 27 days at time of registration.
  4. Obese paediatric patients with body mass index weight (kg)/[height (m)]² > 30 kg/m².
  5. Diagnosis of Fanconi anaemia and other chromosomal breakage disorders, radiosensitivity disorders (deoxyribonucleic acid (DNA) Ligase 4, Cernunnos- X-ray repair cross-complementing protein 4 (XRCC4) like factor (XLF), Nijmegen Breakage Syndrome (NBS)) and Dyskeratosis Congenita.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jochen Kehne, PhD 0049/41038006 ext 388 j.kehne@medac.de
Contact: Kay-Uwe Heuer 0049/41038006 ext 8217 k.heuer@medac.de
Listed Location Countries  ICMJE Austria,   Czechia,   Germany,   Italy,   Poland
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT02349906
Other Study ID Numbers  ICMJE MC-FludT.16/NM
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party medac GmbH
Study Sponsor  ICMJE medac GmbH
Collaborators  ICMJE
  • Celerion
  • Therametrics
  • Syneos Health
Investigators  ICMJE
Principal Investigator: Karl-Walter Sykora, MD and Prof Hannover Medical University
PRS Account medac GmbH
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP