Primary ImmunodeficienciesPhase 2NCT02349906
Treosulfan-based Versus Busulfan-based Conditioning in Paediatric Patients With Non-malignant Diseases
A Phase 2 study testing Treosulfan and Busilvex in people with Primary Immunodeficiencies and Inborn Errors of Metabolism, run by medac GmbH at 21 sites in 4 countries.
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… Read more about this study
- Who is it for?
- Ages 28 days to 17 years
- Conditions the study is for
- Primary Immunodeficiencies, Inborn Errors of Metabolism, Haemoglobinopathies
- What is being tested?
- Treosulfan and Busilvex
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 106 participants
- Where
- 21 sitesin 4 countries
- Study dates
- Apr 2015to 13 Feb 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 28 days to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
21 sites in 4 countries.
21 sites in 4 countries
Italy9 sites
SC Oncoematologia Pediatrica Ospedale Pediatrico Microcitemico "Antonio Cao" A.O. Brotzu
Cagliari, 09121
UOC Ematologia ed Oncologia Pediatrica con TMO AOU Policlinico Vittorio Emanuele
Catania, 95123
Reparto Trapianti Midollo Osseo Clinica Pediatrica Universitaria Fondazione MBBM-Ospedale San Gerardo
Monza, 20900
S.C. Oncoematologia Pediatrica Fondazione IRCCS Policlinico San Matteo
Pavia, 27100
Oncoematologia Pediatrica A.O. di Perugia Ospedale S. Maria della Misericordia
Perugia, 06156
U.O. Oncoematologia Pediatrica Azienda Ospedaliero Universitaria Pisana Ospedale S. Chiara
Pisa, 56100
Ospedale Bambino Gesu Roma
Rome, 00165
Ospedale Infantile Regina Margherita Torino
Turin, 10126
U.O.C. Oncoematologia Pediatrica Policlinico "G.B. Rossi" - AOUI Verona
Verona, 37134
Germany7 sites
Department of Pediatric Oncology & Hematology, Charite Berlin
Berlin, 13353
University Children's Hospital Essen Pediatric stem cell transplantation
Essen, 45122
University Hospital Frankfurt
Frankfurt am Main, 60590
Hannover Medical University, Dep. of Paediatrics, Paediatric Haematology and Oncology
Hanover
Heidelberg University Hospital
Heidelberg, 69120
University of Jena, Department of Pediatrics
Jena, 07747
Ulm, University Hospital, Clinic for Children and Adolescents
Ulm, 89075
Poland4 sites
Szpital Uniwersytecki im. dr Antoniego Jurasza
Bydgoszcz, 85-094
Uniwersytecki Szpital Dzieciecy w Krakowie
Krakow, 30-663
Dzieciecy Szpital Kliniczny im. A. Gebali w Lublinie
Lublin, 20-093
Wroclaw Medical University, Department of Pediatric Hematology/Oncology and BMT
Wroclaw, 50-368
Czechia1 site
University Hospital Motol, Dep. of Paediatric Haematology and Oncology
Prague
About this study
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
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.
Read the 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
- Being tested
- Treosulfan, Busilvex
- Keywords
- non-malignant diseases, allogeneic stem cell transplantation
- Medical subject headings
- Metabolism, Inborn Errors, Hemoglobinopathies, Bone Marrow Failure Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TreosulfanDrug
BusilvexDrug
| Study group | Role | What they receive |
|---|---|---|
| Treosulfan | Experimental | 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. Receives: Drug: Treosulfan |
| Busulfan | Active comparator | 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. Receives: Drug: Busilvex |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: day -7 to day +100
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2015 (estimated)
- Study startApr 2015
- Primary completion7 May 2020
- Study completion13 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary ImmunodeficienciesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 106 participants (actual)
Sponsor and investigators
- Lead sponsor
- medac GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Celerion, Venn Life Sciences, Syneos Health
- Responsible party
- Sponsor
- Investigators
- Karl-Walter Sykora, MD and Prof, Principal investigator, Hannover Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02349906
- Sponsor's protocol ID
- MC-FludT.16/NM
- Status last verified
- Dec 2025
- First submitted
- 26 Jan 2015
- Last updated
- 8 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02349906
- Acronym / sponsor ID
- MC-FludT.16/NM
- Conditions
- Primary Immunodeficiencies, Inborn Errors of Metabolism, Haemoglobinopathies, Bone Marrow Failure Syndromes
- Keywords
- non-malignant diseases, allogeneic stem cell transplantation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 106 participants (actual)
- Lead sponsor
- medac GmbHIndustry (pharma, biotech, devices)
- Collaborators
- Celerion, Venn Life Sciences, Syneos Health
- Study start
- Apr 2015
- Primary completion
- 7 May 2020 (actual)
- Study completion
- 13 Feb 2023 (actual)
- First posted
- 29 Jan 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treosulfan | Experimental | Drug: TreosulfanOne 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. |
| Busulfan | Active comparator | Drug: BusilvexTotal 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. |
Who may qualify
- Ages
- 28 days to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Treosulfan | Drug | Treosulfan |
| Busilvex | Drug | Busulfan |
Primary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Dec 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Karl-Walter Sykora, MD and Prof principal investigator
Hannover Medical University
21 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Treosulfan and Busilvex in people with Primary Immunodeficiencies and Inborn Errors of Metabolism, run by medac GmbH at 21 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in Italy, Germany, Poland, Czechia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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. (time frame: day -7 to day +100). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Dec 2025.