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

Inborn Errors of Metabolism Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02349906
• Other study ID #: MC-FludT.16/NM
• Status: Completed
• Phase: Phase 2
• Start date: April 2015
• Est. completion date: April 2023

Study information

• Verified date: November 2023
• Source: medac GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 106
• Est. completion date: April 2023
• Est. primary completion date: May 7, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 28 Days to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Bone Marrow Failure Disorders
• Bone Marrow Failure Syndromes
• Haemoglobinopathies
• Hemoglobinopathies
• Inborn Errors of Metabolism
• Metabolism, Inborn Errors
• Pancytopenia
• Primary Immunodeficiencies
• Primary Immunodeficiency Diseases

Intervention

Drug:
• Treosulfan

• Busilvex

Locations

Country	Name	City	State
Czechia	University Hospital Motol, Dep. of Paediatric Haematology and Oncology	Prague
Germany	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	Hannover
Germany	Heidelberg University Hospital	Heidelberg
Germany	University of Jena, Department of Pediatrics	Jena
Germany	Ulm, University Hospital, Clinic for Children and Adolescents	Ulm
Italy	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
Poland	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

Sponsors (4)

Lead Sponsor	Collaborator
medac GmbH	Celerion, Syneos Health, Venn Life Sciences

Countries where clinical trial is conducted

Czechia,  Germany,  Italy,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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