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

NCT ID: NCT02349906

Last Updated: 2025-12-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 106 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-30
• Study Completion Date: 2023-02-13

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Treosulfan

Intervention Type: DRUG

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.

Group Type: ACTIVE_COMPARATOR

Busilvex

Intervention Type: DRUG

Interventions

Treosulfan

Intervention Type: DRUG

Busilvex

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 28 Days
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celerion

INDUSTRY

Sponsor Role: collaborator

Venn Life Sciences

OTHER

Sponsor Role: collaborator

Syneos Health

OTHER

Sponsor Role: collaborator

medac GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Karl-Walter Sykora, MD and Prof

Role: PRINCIPAL_INVESTIGATOR

Hannover Medical University

Locations

University Hospital Motol, Dep. of Paediatric Haematology and Oncology

Prague, , Czechia

Department of Pediatric Oncology & Hematology, Charite Berlin

Berlin, , Germany

University Children's Hospital Essen Pediatric stem cell transplantation

Essen, , Germany

University Hospital Frankfurt

Frankfurt am Main, , Germany

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

Hanover, , Germany

Heidelberg University Hospital

Heidelberg, , Germany

University of Jena, Department of Pediatrics

Jena, , Germany

Ulm, University Hospital, Clinic for Children and Adolescents

Ulm, , Germany

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

Cagliari, , Italy

UOC Ematologia ed Oncologia Pediatrica con TMO AOU Policlinico Vittorio Emanuele

Catania, , Italy

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

Monza, , Italy

S.C. Oncoematologia Pediatrica Fondazione IRCCS Policlinico San Matteo

Pavia, , Italy

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

Perugia, , Italy

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

Pisa, , Italy

Ospedale Bambino Gesu Roma

Rome, , Italy

Ospedale Infantile Regina Margherita Torino

Turin, , Italy

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

Verona, , Italy

Szpital Uniwersytecki im. dr Antoniego Jurasza

Bydgoszcz, , Poland

Uniwersytecki Szpital Dzieciecy w Krakowie

Krakow, , Poland

Dzieciecy Szpital Kliniczny im. A. Gebali w Lublinie

Lublin, , Poland

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

Wroclaw, , Poland

Countries

Czechia; Germany; Italy; Poland

Other Identifiers

MC-FludT.16/NM

Identifier Type: -

Identifier Source: org_study_id