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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 : Active, not recruiting
First Posted : January 29, 2015
Last Update Posted : April 20, 2022
Venn Life Sciences
Syneos Health
Information provided by (Responsible Party):
medac GmbH

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.

Condition or disease Intervention/treatment Phase
Primary Immunodeficiencies Inborn Errors of Metabolism Haemoglobinopathies Bone Marrow Failure Syndromes Drug: Treosulfan Drug: Busilvex Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 106 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : April 2015
Actual Primary Completion Date : May 7, 2020
Estimated Study Completion Date : January 2023

Arm Intervention/treatment
Experimental: Treosulfan

One Treosulfan dose per day administered i.v. on three consecutive days (-6, -5 and -4); given over 2 hours as part of background conditioning prior to allogeneic stem cell transplantation.

The dose has to be calculated as follows:

If the BSA (m2) is equal or less than 0.3, the Treosulfan dose should be 10g/m2/day.

If the BSA (m2) is greater than 0.3 and equal or less than 0.8, the Treosulfan dose should be 12g/m2/day.

If the BSA (m2) is greater than 0.8, the Treosulfan dose should be 14g/m2/day.

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.
Drug: Busilvex

Primary Outcome Measures :
  1. 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 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   28 Days to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

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): NCT02349906

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Sponsors and Collaborators
medac GmbH
Venn Life Sciences
Syneos Health
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Principal Investigator: Karl-Walter Sykora, MD and Prof Hannover Medical University
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Responsible Party: medac GmbH
ClinicalTrials.gov Identifier: NCT02349906    
Other Study ID Numbers: MC-FludT.16/NM
First Posted: January 29, 2015    Key Record Dates
Last Update Posted: April 20, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by medac GmbH:
non-malignant diseases, allogeneic stem cell transplantation
Additional relevant MeSH terms:
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Bone Marrow Failure Disorders
Primary Immunodeficiency Diseases
Metabolism, Inborn Errors
Immunologic Deficiency Syndromes
Immune System Diseases
Genetic Diseases, Inborn
Hematologic Diseases
Bone Marrow Diseases
Metabolic Diseases
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents