Treosulfan-based Versus Busulfan-based Conditioning in Paediatric Patients With Non-malignant Diseases

NCT02349906 | Completed Phase 2 DMC

• 1 other identifier: MC-FludT.16/NM
• Study Type: interventional
• Target: 106
• Locations: 4 countries
• Sites: 21

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.

Conditions

Primary Immunodeficiencies; Inborn Errors of Metabolism; Haemoglobinopathies; Bone Marrow Failure Syndromes

Keywords

non-malignant diseases, allogeneic stem cell transplantation

Outcome Measures

Primary Outcomes (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.

  day -7 to day +100

Study Arms (2)

Treosulfan

EXPERIMENTAL

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

Busulfan

ACTIVE COMPARATOR

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

Interventions

Treosulfan DRUG

Treosulfan

Busilvex DRUG

Busulfan

Eligibility Criteria

• Age: 28 Days - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Non-malignant disease indicated for first myeloablative allogeneic HSCT, including inborn errors of metabolism, primary immunodeficiencies, haemoglobinopathies and bone marrow failure syndromes.
• First allogeneic HSCT.
• 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.

You may not qualify if:

• Second or later HSCT.
• HSCT from mismatched donor (less than 9/10 BM/peripheral blood stem cells (PBSC) or less than 5/6 matched cord donor).
• Preterm newborn infants (\<37 weeks gestational age) and term newborn infants aged 0 - 27 days at time of registration.
• Obese paediatric patients with body mass index weight (kg)/\[height (m)\]² \> 30 kg/m².
• 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.

Sponsors & Collaborators

• medac GmbH: lead
• Celerion: collaborator
• Venn Life Sciences: collaborator
• Syneos Health: collaborator

Study Sites (21)

University Hospital Motol, Dep. of Paediatric Haematology and Oncology

Prague, Czechia

Location

Department of Pediatric Oncology & Hematology, Charite Berlin

Berlin, 13353, Germany

Location

University Children's Hospital Essen Pediatric stem cell transplantation

Essen, 45122, Germany

Location

University Hospital Frankfurt

Frankfurt am Main, 60590, Germany

Location

Hannover Medical University, Dep. of Paediatrics, Paediatric Haematology and Oncology

Hanover, Germany

Location

Heidelberg University Hospital

Heidelberg, 69120, Germany

Location

University of Jena, Department of Pediatrics

Jena, 07747, Germany

Location

Ulm, University Hospital, Clinic for Children and Adolescents

Ulm, 89075, Germany

Location

SC Oncoematologia Pediatrica Ospedale Pediatrico Microcitemico "Antonio Cao" A.O. Brotzu

Cagliari, 09121, Italy

Location

UOC Ematologia ed Oncologia Pediatrica con TMO AOU Policlinico Vittorio Emanuele

Catania, 95123, Italy

Location

Reparto Trapianti Midollo Osseo Clinica Pediatrica Universitaria Fondazione MBBM-Ospedale San Gerardo

Monza, 20900, Italy

Location

S.C. Oncoematologia Pediatrica Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, Italy

Location

Oncoematologia Pediatrica A.O. di Perugia Ospedale S. Maria della Misericordia

Perugia, 06156, Italy

Location

U.O. Oncoematologia Pediatrica Azienda Ospedaliero Universitaria Pisana Ospedale S. Chiara

Pisa, 56100, Italy

Location

Ospedale Bambino Gesu Roma

Rome, 00165, Italy

Location

Ospedale Infantile Regina Margherita Torino

Turin, 10126, Italy

Location

U.O.C. Oncoematologia Pediatrica Policlinico "G.B. Rossi" - AOUI Verona

Verona, 37134, Italy

Location

Szpital Uniwersytecki im. dr Antoniego Jurasza

Bydgoszcz, 85-094, Poland

Location

Uniwersytecki Szpital Dzieciecy w Krakowie

Krakow, 30-663, Poland

Location

Dzieciecy Szpital Kliniczny im. A. Gebali w Lublinie

Lublin, 20-093, Poland

Location

Wroclaw Medical University, Department of Pediatric Hematology/Oncology and BMT

Wroclaw, 50-368, Poland

Location

MeSH Terms

Conditions

Metabolism, Inborn Errors; Hemoglobinopathies; Bone Marrow Failure Disorders

Interventions

treosulfan; Busulfan

Condition Hierarchy (Ancestors)

Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Karl-Walter Sykora, MD and Prof

  Hannover Medical University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2015
• First Posted: January 29, 2015
• Study Start: April 1, 2015
• Primary Completion: May 7, 2020
• Study Completion: February 13, 2023
• Last Updated: December 8, 2025

Record last verified: 2025-12

Locations

IT (9); CZ (1); DE (7); PL (4)