Clinical trial NCT02349906: Treosulfan-based Versus Busulfan-based Conditioning in Paediatric Patients With Non-malignant Diseases
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Primary Immunodeficiencies
Inborn Errors of Metabolism
Haemoglobinopathies
Bone Marrow Failure Syndromes
Keywords: non-malignant diseases, allogeneic stem cell transplantation
Lead sponsor: medac GmbH
Sponsor class: INDUSTRY
Collaborators: name: Celerion
name: Venn Life Sciences
name: Syneos Health
First posted: 2015-01-29
Enrollment: 106
Sex: ALL
Minimum age (years): 28
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: 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.
timeFrame: day -7 to day +100
Secondary outcomes:
Other outcomes:
Locations:
city: Prague
country: Czechia
facility: University Hospital Motol, Dep. of Paediatric Haematology and Oncology
city: Berlin
country: Germany
facility: Department of Pediatric Oncology & Hematology, Charite Berlin
city: Essen
country: Germany
facility: University Children's Hospital Essen Pediatric stem cell transplantation
city: Frankfurt am Main
country: Germany
facility: University Hospital Frankfurt
city: Hannover
country: Germany
facility: Hannover Medical University, Dep. of Paediatrics, Paediatric Haematology and Oncology
city: Heidelberg
country: Germany
facility: Heidelberg University Hospital
city: Jena
country: Germany
facility: University of Jena, Department of Pediatrics
city: Ulm
country: Germany
facility: Ulm, University Hospital, Clinic for Children and Adolescents
city: Cagliari
country: Italy
facility: SC Oncoematologia Pediatrica Ospedale Pediatrico Microcitemico "Antonio Cao" A.O. Brotzu
city: Catania
country: Italy
facility: UOC Ematologia ed Oncologia Pediatrica con TMO AOU Policlinico Vittorio Emanuele
city: Monza
country: Italy
facility: Reparto Trapianti Midollo Osseo Clinica Pediatrica Universitaria Fondazione MBBM-Ospedale San Gerardo
city: Pavia
country: Italy
facility: S.C. Oncoematologia Pediatrica Fondazione IRCCS Policlinico San Matteo
city: Perugia
country: Italy
facility: Oncoematologia Pediatrica A.O. di Perugia Ospedale S. Maria della Misericordia
city: Pisa
country: Italy
facility: U.O. Oncoematologia Pediatrica Azienda Ospedaliero Universitaria Pisana Ospedale S. Chiara
city: Rome
country: Italy
facility: Ospedale Bambino Gesu Roma
city: Turin
country: Italy
facility: Ospedale Infantile Regina Margherita Torino
city: Verona
country: Italy
facility: U.O.C. Oncoematologia Pediatrica Policlinico "G.B. Rossi" - AOUI Verona
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki im. dr Antoniego Jurasza
city: Krakow
country: Poland
facility: Uniwersytecki Szpital Dzieciecy w Krakowie
city: Lublin
country: Poland
facility: Dzieciecy Szpital Kliniczny im. A. Gebali w Lublinie
city: Wroclaw
country: Poland
facility: Wroclaw Medical University, Department of Pediatric Hematology/Oncology and BMT
Study officials:
affiliation: Hannover Medical University
name: Karl-Walter Sykora, MD and Prof
role: PRINCIPAL_INVESTIGATOR
References: