- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02349906
Treosulfan-based Versus Busulfan-based Conditioning in Paediatric Patients With Non-malignant Diseases
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 Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
-
Prague, Czechia
- University Hospital Motol, Dep. of Paediatric Haematology and Oncology
-
-
-
-
-
Berlin, Germany, 13353
- Department of Pediatric Oncology & Hematology, Charite Berlin
-
Essen, Germany, 45122
- University Children's Hospital Essen Pediatric stem cell transplantation
-
Frankfurt am Main, Germany, 60590
- University Hospital Frankfurt
-
Hannover, Germany
- Hannover Medical University, Dep. of Paediatrics, Paediatric Haematology and Oncology
-
Heidelberg, Germany, 69120
- Heidelberg University Hospital
-
Jena, Germany, 07747
- University of Jena, Department of Pediatrics
-
Ulm, Germany, 89075
- Ulm, University Hospital, Clinic for Children and Adolescents
-
-
-
-
-
Cagliari, Italy, 09121
- SC Oncoematologia Pediatrica Ospedale Pediatrico Microcitemico "Antonio Cao" A.O. Brotzu
-
Catania, Italy, 95123
- UOC Ematologia ed Oncologia Pediatrica con TMO AOU Policlinico Vittorio Emanuele
-
Monza, Italy, 20900
- Reparto Trapianti Midollo Osseo Clinica Pediatrica Universitaria Fondazione MBBM-Ospedale San Gerardo
-
Pavia, Italy, 27100
- S.C. Oncoematologia Pediatrica Fondazione IRCCS Policlinico San Matteo
-
Perugia, Italy, 06156
- Oncoematologia Pediatrica A.O. di Perugia Ospedale S. Maria della Misericordia
-
Pisa, Italy, 56100
- U.O. Oncoematologia Pediatrica Azienda Ospedaliero Universitaria Pisana Ospedale S. Chiara
-
Rome, Italy, 00165
- Ospedale Bambino Gesu Roma
-
Turin, Italy, 10126
- Ospedale Infantile Regina Margherita Torino
-
Verona, Italy, 37134
- U.O.C. Oncoematologia Pediatrica Policlinico "G.B. Rossi" - AOUI Verona
-
-
-
-
-
Bydgoszcz, Poland, 85-094
- Szpital Uniwersytecki im. dr Antoniego Jurasza
-
Krakow, Poland, 30-663
- Uniwersytecki Szpital Dzieciecy w Krakowie
-
Lublin, Poland, 20-093
- Dzieciecy Szpital Kliniczny im. A. Gebali w Lublinie
-
Wroclaw, Poland, 50-368
- Wroclaw Medical University, Department of Pediatric Hematology/Oncology and BMT
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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. |
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
|
day -7 to day +100
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Karl-Walter Sykora, MD and Prof, Hannover Medical University
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Metabolic Diseases
- Immunologic Deficiency Syndromes
- Immune System Diseases
- Bone Marrow Diseases
- Hematologic Diseases
- Genetic Diseases, Inborn
- Primary Immunodeficiency Diseases
- Metabolism, Inborn Errors
- Hemoglobinopathies
- Bone Marrow Failure Disorders
- Pancytopenia
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Treosulfan
Other Study ID Numbers
- MC-FludT.16/NM
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Bone Marrow Failure Syndromes
-
Sohag UniversityAssiut University; Kyoto UniversityRecruitingInherited BMF SyndromeEgypt
-
Cellenkos, Inc.Active, not recruitingBone Marrow DiseaseUnited States
-
Medical College of WisconsinChildren's Hospital of PhiladelphiaCompletedMalignant Diseases (ie, Leukemia, MDS, Lymphoma) | Non-malignant Diseases (ie, Bone Marrow Failure Syndromes)United States
-
Children's Hospital of PhiladelphiaAvailableLeukemia | Immunodeficiencies | Bone Marrow Failure SyndromeUnited States
-
University of CalgaryUnknownBone Marrow Failure Syndrome
-
St. Jude Children's Research HospitalActive, not recruitingAplastic Anemia | Bone Marrow Failure SyndromeUnited States
-
National Cancer Institute (NCI)RecruitingInherited Bone Marrow Failure Syndrome | Familial Platelet Disorder With Predisposition to Myeloid MalignanciesUnited States
-
Rabin Medical CenterUnknownHematological Malignancy | Bone Marrow Failure SyndromeIsrael
-
Children's Hospital of PhiladelphiaCompletedBone Marrow Failure Syndromes | Immunodeficiencies | Immune Dysregulation SyndromesUnited States
-
Franziska WachterHarvard Clinical and Translational Science Center (Harvard Catalyst)RecruitingAcute Myeloid Leukemia | Myelodysplastic Syndromes | MDS | Aml | Myeloid Neoplasm | Myeloid Malignancies | Inherited Bone Marrow Failure SyndromeUnited States
Clinical Trials on Treosulfan
-
Sheba Medical CenterUnknownHodgkin Lymphoma | Non Hodgkin LymphomaIsrael
-
IRCCS San RaffaeleUnknownLeukemia | Multiple Myeloma | Hodgkin Lymphoma | Chronic Lymphocytic Leukemia | Chronic Myeloid Leukemia | Myelodysplastic Syndrome | Diffuse Large Cell LymphomaItaly
-
Hospices Civils de LyonUnknownHematological Malignancies | Allogeneic TransplantationFrance
-
OHSU Knight Cancer InstituteNational Cancer Institute (NCI); medac GmbHCompletedMyelodysplastic Syndromes | LeukemiaUnited States
-
IRCCS San RaffaeleTerminatedMultiple Myeloma | Graft Vs Host Disease | Leukemia, Acute | Transplant-Related Hematologic Malignancy | Irradiated Bone MarrowItaly
-
Dr. Avichai Shimoni MDCompletedAcute Myeloid Leukemia | Myelodysplastic SyndromeIsrael
-
Great Ormond Street Hospital for Children NHS Foundation...Newcastle-upon-Tyne Hospitals NHS TrustCompletedAllogeneic Haematopoietic Stem Cell TransplantationUnited Kingdom
-
Center for International Blood and Marrow Transplant...National Marrow Donor Program; Pediatric Blood and Marrow Transplant Consortium and other collaboratorsCompletedAcute Myeloid Leukemia (AML) | Myelodysplastic Syndrome (MDS)United States
-
medac GmbHCompleted
-
medac GmbHCompleted