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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02349906
Recruitment Status : Recruiting
First Posted : January 29, 2015
Last Update Posted : August 16, 2018
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)
Estimated Enrollment : 100 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
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2019

Arm Intervention/treatment
Experimental: Treosulfan
One Treosulfan dose per day (10, 12 or 14 g/m2/day, based on body surface area) administered i.v. on three consecutive days (-6, -5 and -4); given over 2 hours as part of background conditioning regimen prior to allogeneic stem cell transplantation.
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:   up 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 identifier (NCT number): NCT02349906

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Contact: Jochen Kehne, PhD 0049/41038006 ext 388
Contact: Kay-Uwe Heuer 0049/41038006 ext 8217

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St. Anna Children's Hospital Withdrawn
Vienna, Austria, 1090
University Hospital Motol, Dep. of Paediatric Haematology and Oncology Recruiting
Prague, Czechia
Contact: Petr Sedlacek, MD, Prof.    +42060672 ext 6550      
Department of Pediatric Oncology & Hematology, Charite Berlin Not yet recruiting
Berlin, Germany, 13353
Contact: Johannes Schulte, MD, Prof.         
Duesseldorf University Hospital Withdrawn
Duesseldorf, Germany, 40225
University Children's Hospital Essen Pediatric stem cell transplantation Not yet recruiting
Essen, Germany, 45122
Contact: Rita Beier, MD         
University Hospital Frankfurt Recruiting
Frankfurt am Main, Germany, 60590
Contact: Peter Bader, MD, Prof.         
University Medical Center Hamburg-Eppendorf Withdrawn
Hamburg, Germany, 20246
Hannover Medical University, Dep. of Paediatrics, Paediatric Haematology and Oncology Recruiting
Hannover, Germany
Contact: Karl-Walter Sykora, MD, Prof.    +49(0)511532 ext 5830      
Heidelberg University Hospital Recruiting
Heidelberg, Germany, 69120
Contact: Johann Greil, MD, Prof.         
University of Jena, Department of Pediatrics Not yet recruiting
Jena, Germany, 07747
Contact: Bernd Gruhn, MD, Prof.         
University Hospital Regensburg Withdrawn
Regensburg, Germany, 93053
Ulm, University Hospital, Clinic for Children and Adolescents Recruiting
Ulm, Germany, 89075
Contact: Ansgar Schulz, MD, Prof.    +49(0)731500 ext 57154      
University Hospital of Wuerzburg Withdrawn
Wuerzburg, Germany, 97080
SC Oncoematologia Pediatrica Ospedale Pediatrico Microcitemico "Antonio Cao" A.O. Brotzu Not yet recruiting
Cagliari, Italy, 09121
Contact: Maria Grazia Orofino, MD         
UOC Ematologia ed Oncologia Pediatrica con TMO AOU Policlinico Vittorio Emanuele Not yet recruiting
Catania, Italy, 95123
Contact: Giovanna Russo, MD         
Reparto Trapianti Midollo Osseo Clinica Pediatrica Universitaria Fondazione MBBM-Ospedale San Gerardo Not yet recruiting
Monza, Italy, 20900
Contact: Sonia Bonanomi, MD         
S.C. Oncoematologia Pediatrica Fondazione IRCCS Policlinico San Matteo Not yet recruiting
Pavia, Italy, 27100
Contact: Marco Zecca, MD         
Oncoematologia Pediatrica A.O. di Perugia Ospedale S. Maria della Misericordia Not yet recruiting
Perugia, Italy, 06156
Contact: Maurizio Caniglia, MD         
U.O. Oncoematologia Pediatrica Azienda Ospedaliero Universitaria Pisana Ospedale S. Chiara Not yet recruiting
Pisa, Italy, 56100
Contact: Mariacristina Menconi, MD         
Ospedale Bambino Gesu Roma Recruiting
Rome, Italy, 00165
Contact: Franco Locatelli, MD, Prof.         
Ospedale Infantile Regina Margherita Torino Recruiting
Turin, Italy, 10126
Contact: Franca Fagioli, MD, Prof.         
U.O.C. Oncoematologia Pediatrica Policlinico "G.B. Rossi" - AOUI Verona Recruiting
Verona, Italy, 37134
Contact: Simone Cesaro, MD         
Szpital Uniwersytecki im. dr Antoniego Jurasza Recruiting
Bydgoszcz, Poland, 85-094
Contact: Jan Styczynski, MD, Prof         
Uniwersytecki Szpital Dzieciecy w Krakowie Recruiting
Krakow, Poland, 30-663
Contact: Jolanta Gozdzik, MD         
Dzieciecy Szpital Kliniczny im. A. Gebali w Lublinie Not yet recruiting
Lublin, Poland, 20-093
Contact: Katarzyna Drabko, MD         
Wroclaw Medical University, Department of Pediatric Hematology/Oncology and BMT Recruiting
Wroclaw, Poland, 50-368
Contact: Krzysztof Kałwak, MD, PhD, Prof.    (48)-71 ext 7703170      
Sponsors and Collaborators
medac GmbH
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 Identifier: NCT02349906     History of Changes
Other Study ID Numbers: MC-FludT.16/NM
First Posted: January 29, 2015    Key Record Dates
Last Update Posted: August 16, 2018
Last Verified: August 2018
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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Anemia, Aplastic
Hemoglobinuria, Paroxysmal
Metabolism, Inborn Errors
Immunologic Deficiency Syndromes
Immune System Diseases
Hematologic Diseases
Genetic Diseases, Inborn
Metabolic Diseases
Bone Marrow Diseases
Anemia, Hemolytic
Myelodysplastic Syndromes
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Antineoplastic Agents
Myeloablative Agonists