Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
UNKNOWN
PHASE2
130 participants
INTERVENTIONAL
2011-09-30
2016-10-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
The conditioning proposed combines myeloablative drugs with a favorable safety profile such as treosulfan, thiotepa (Tepadina®) and fludarabine with the intent to reduce the traditional immediate and late toxicity of busulfan and cyclophosphamide.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Rituximab in Treating Patients Undergoing Donor Peripheral Blood Stem Cell Transplant for Relapsed or Refractory B-cell Lymphoma
NCT00867529
Ph II of Non-myeloablative Allogeneic Transplantation Using TLI & ATG In Patients w/ Cutaneous T Cell Lymphoma
NCT00896493
Yttrium Y 90 Ibritumomab Tiuxetan, Fludarabine, Radiation Therapy, and Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma
NCT00119392
A Study of YM155 Plus Rituximab in Subjects With Non-Hodgkin's Lymphoma Who Have Received Prior Treatment
NCT01007292
Radioimmunotherapy in Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma
NCT00005592
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
The primary end-point is the cumulative incidence of a combined end-point defined as the time from randomization to:
* primary and secondary graft failure,
* aGVHD II-IV,
* cGVHD,
* death, whichever occurs first.
For patients transplanted from a MUD
The primary end-point is the cumulative incidence of a combined end-point defined as the time from randomization to:
* aGVHD II-IV,
* EBV viremia, whichever occurs first.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
PREVENTION
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
MRD-Regimen&Polyclonal antibody
Patients MRD will be randomized to receive Treosulfan iv at a dose of 14 g/m² within 120 minutes on day -7, - 6, -5 + Fludarabine iv at a dose of 30 mg/ m² within 30 minutes on day -7, -6, -5,-4,-3 after treosulfan + Thiotepa iv at a dose of 8 mg/kg on day - 3 divided into 2 infusions at 12 hrs intervals + Cyclosporine A iv at a dose of 3 mg/kg/day starting from day -1 and a dose adjustment will be done to obtain plasma levels of 150-250 ng/mL + Methotrexate iv at a dose of 15 mg/m2 on day +1, at a dose of 10 mg/m2 on day + 3 and + 6 \& ATG-Fresenius S® iv at a dose of 5 mg/kg within 8 hours on day -4,-3,-2
polyclonal antibody
iv at a dose of 5 mg/kg within 8 hours on day -4,-3,-2 (total dose 15 mg/kg)
Treosulfan
iv at a dose of 14 g/m² within 120 minutes on day -7, - 6, -5 (total dose of 42 g/m²)
Fludarabine
iv at a dose of 30 mg/ m² within 30 minutes on day -7, -6, -5,-4,-3 after treosulfan
Thiotepa
iv at a dose of 8 mg/kg on day - 3 divided into 2 infusions at 12 hrs intervals
Cyclosporine A
iv at a dose of 3 mg/kg/day starting from day -1 and a dose adjustment will be done to obtain plasma levels of 150-250 ng/mL
Methotrexate
iv at a dose of 15 mg/m2 on day +1, at a dose of 10 mg/m2 on day + 3 and + 6
MRD-Regimen
Patients receiving stem cell transplantation from a matched related donors (MRD) will be randomized to receive only Treosulfan iv at a dose of 14 g/m² within 120 minutes on day -7, - 6, -5 (total dose of 42 g/m²) + Fludarabine iv at a dose of 30 mg/ m² within 30 minutes on day -7, -6, -5,-4,-3 (total dose of 150 mg/m²) after treosulfan + Thiotepa iv at a dose of 8 mg/kg on day - 3 divided into 2 infusions at 12 hrs intervals (total dose of 8 mg/kg)+ Cyclosporine A iv at a starting dose of 3 mg/kg/day starting from day -1 and a dose adjustment will be done to obtain plasma levels of 150-250 ng/mL (In the absence of GvHD CSA will be tapered after day + 180 and stopped at 9-12 months) + Methotrexate iv at a dose of 15 mg/m2 on day +1, at a dose of 10 mg/m2 on day + 3 and + 6
Treosulfan
iv at a dose of 14 g/m² within 120 minutes on day -7, - 6, -5 (total dose of 42 g/m²)
Fludarabine
iv at a dose of 30 mg/ m² within 30 minutes on day -7, -6, -5,-4,-3 after treosulfan
Thiotepa
iv at a dose of 8 mg/kg on day - 3 divided into 2 infusions at 12 hrs intervals
Cyclosporine A
iv at a dose of 3 mg/kg/day starting from day -1 and a dose adjustment will be done to obtain plasma levels of 150-250 ng/mL
Methotrexate
iv at a dose of 15 mg/m2 on day +1, at a dose of 10 mg/m2 on day + 3 and + 6
MUD-Regimen & Rituximab
Patients MUD will be randomized to receive Treosulfan iv at a dose of 14 g/m² within 120 minutes on day -7, - 6, -5 + Fludarabine iv at a dose of 30 mg/ m² within 30 minutes on day -7, -6, -5,-4,-3 after treosulfan + Thiotepa iv at a dose of 8 mg/kg on day - 3 divided into 2 infusions at 12 hrs intervals + Cyclosporine A iv at a dose of 3 mg/kg/day starting from day -1 and a dose adjustment will be done to obtain plasma levels of 150-250 ng/mL + Methotrexate iv at a dose of 15 mg/m2 on day +1, at a dose of 10 mg/m2 on day + 3 and + 6 and at a dose of 10 mg/m2 on day +11 + ATG-Fresenius S ® iv at a dose of 5 mg/kg within 8 hours on day -4,-3,-2 \& Rituximab in a single infusion of 200 mg/m2 on day -1
polyclonal antibody
iv at a dose of 5 mg/kg within 8 hours on day -4,-3,-2 (total dose 15 mg/kg)
Rituximab
single infusion of200 mg/m2 on day -1
Treosulfan
iv at a dose of 14 g/m² within 120 minutes on day -7, - 6, -5 (total dose of 42 g/m²)
Fludarabine
iv at a dose of 30 mg/ m² within 30 minutes on day -7, -6, -5,-4,-3 after treosulfan
Thiotepa
iv at a dose of 8 mg/kg on day - 3 divided into 2 infusions at 12 hrs intervals
Cyclosporine A
iv at a dose of 3 mg/kg/day starting from day -1 and a dose adjustment will be done to obtain plasma levels of 150-250 ng/mL
Methotrexate
iv at a dose of 15 mg/m2 on day +1, at a dose of 10 mg/m2 on day + 3 and + 6 and at a dose of 10 mg/m2 on day +11
MUD-Regimen
Patients MUD will be randomized to receive only Treosulfan iv at a dose of 14 g/m² within 120 minutes on day -7, - 6, -5 + Fludarabine iv at a dose of 30 mg/ m² within 30 minutes on day -7, -6, -5,-4,-3 after treosulfan + Thiotepa iv at a dose of 8 mg/kg on day - 3 divided into 2 infusions at 12 hrs intervals + Cyclosporine A iv at a dose of 3 mg/kg/day starting from day -1 and a dose adjustment will be done to obtain plasma levels of 150-250 ng/mL + Methotrexate iv at a dose of 15 mg/m2 on day +1, at a dose of 10 mg/m2 on day + 3 and + 6 and at a dose of 10 mg/m2 on day +11 + ATG-Fresenius S ® iv at a dose of 5 mg/kg within 8 hours on day -4,-3,-2
polyclonal antibody
iv at a dose of 5 mg/kg within 8 hours on day -4,-3,-2 (total dose 15 mg/kg)
Treosulfan
iv at a dose of 14 g/m² within 120 minutes on day -7, - 6, -5 (total dose of 42 g/m²)
Fludarabine
iv at a dose of 30 mg/ m² within 30 minutes on day -7, -6, -5,-4,-3 after treosulfan
Thiotepa
iv at a dose of 8 mg/kg on day - 3 divided into 2 infusions at 12 hrs intervals
Cyclosporine A
iv at a dose of 3 mg/kg/day starting from day -1 and a dose adjustment will be done to obtain plasma levels of 150-250 ng/mL
Methotrexate
iv at a dose of 15 mg/m2 on day +1, at a dose of 10 mg/m2 on day + 3 and + 6 and at a dose of 10 mg/m2 on day +11
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
polyclonal antibody
iv at a dose of 5 mg/kg within 8 hours on day -4,-3,-2 (total dose 15 mg/kg)
Rituximab
single infusion of200 mg/m2 on day -1
Treosulfan
iv at a dose of 14 g/m² within 120 minutes on day -7, - 6, -5 (total dose of 42 g/m²)
Fludarabine
iv at a dose of 30 mg/ m² within 30 minutes on day -7, -6, -5,-4,-3 after treosulfan
Thiotepa
iv at a dose of 8 mg/kg on day - 3 divided into 2 infusions at 12 hrs intervals
Cyclosporine A
iv at a dose of 3 mg/kg/day starting from day -1 and a dose adjustment will be done to obtain plasma levels of 150-250 ng/mL
Methotrexate
iv at a dose of 15 mg/m2 on day +1, at a dose of 10 mg/m2 on day + 3 and + 6
Methotrexate
iv at a dose of 15 mg/m2 on day +1, at a dose of 10 mg/m2 on day + 3 and + 6 and at a dose of 10 mg/m2 on day +11
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Availability of a matched related donor (MRD) or Matched Unrelated Donor (MUD)
* Lansky or Karnofsky Index ≥ 60
* Inherited metabolic disorders: DQ ≥ 70 (+ MRI Loes score ≤ 9 for adrenoleukodystrophy)
* Adequate cardiac, renal, hepatic and pulmonary functions as evidenced by:
* Serum creatinine ≤ 1.5 × upper limit of normal (ULN)
* Heart shortening fraction (left-ventricle) \> 28 % or LVEF \> 55%
* Serum bilirubin ≤ 1.5 × ULN (except for Wolman disease),
* AST and ALT ≤ 2.5 × ULN (except for thalassemic syndromes and Wolman disease)
* Pulmonary function: if cooperative: FEV1 and FVC on pulmonary function testing \> 60 %; if non cooperative: pulse oximetry \> 95 % in room air
* Availability of autologous back up marrow (\> 2 x 108 TNC+ cells/kg or \> 2 x 106 CD34+ cells/kg) for MUD
* Adequate contraception in female patients of child-bearing potential
* Signed informed consent
Exclusion Criteria
* Liver cirrhosis evidenced on liver histology (performed in suspicious cases or in case of Wolman disease)
* HIV- positivity
* Clinically significant pleural effusion or ascites
* Pregnancy or lactation
* Known hypersensitivity to trial drugs
* Participation in another experimental drug trial in the 2 months preceding enrollment
* Non-cooperative behaviour or non-compliance
* Previous HSCT
28 Days
64 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
University of Milano Bicocca
OTHER
medac GmbH
INDUSTRY
Fresenius AG
INDUSTRY
Franco Locatelli
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Franco Locatelli
Director Department of Pediatric Hematology and Oncology
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Franco Locatelli, Prof
Role: PRINCIPAL_INVESTIGATOR
Bambino Gesù Hospital and Research Institute
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
University of Cagliari
Cagliari, Italy, Italy
San Raffaele Scientific Institute
Milan, Italy, Italy
University of Milano-Bicocca San Gerardo Hospital
Monza, Italy, Italy
Bambino Gesù Hospital and Research Institute
Rome, Italy, Italy
Countries
Review the countries where the study has at least one active or historical site.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
References
Explore related publications, articles, or registry entries linked to this study.
Bacigalupo A, Lamparelli T, Barisione G, Bruzzi P, Guidi S, Alessandrino PE, di Bartolomeo P, Oneto R, Bruno B, Sacchi N, van Lint MT, Bosi A; Gruppo Italiano Trapianti Midollo Osseo (GITMO). Thymoglobulin prevents chronic graft-versus-host disease, chronic lung dysfunction, and late transplant-related mortality: long-term follow-up of a randomized trial in patients undergoing unrelated donor transplantation. Biol Blood Marrow Transplant. 2006 May;12(5):560-5. doi: 10.1016/j.bbmt.2005.12.034.
Bacigalupo A, Lamparelli T, Bruzzi P, Guidi S, Alessandrino PE, di Bartolomeo P, Oneto R, Bruno B, Barbanti M, Sacchi N, Van Lint MT, Bosi A. Antithymocyte globulin for graft-versus-host disease prophylaxis in transplants from unrelated donors: 2 randomized studies from Gruppo Italiano Trapianti Midollo Osseo (GITMO). Blood. 2001 Nov 15;98(10):2942-7. doi: 10.1182/blood.v98.10.2942.
Ballet JJ, Griscelli C, Coutris C, Milhaud G, Maroteaux P. Bone-marrow transplantation in osteopetrosis. Lancet. 1977 Nov 26;2(8048):1137. doi: 10.1016/s0140-6736(77)90592-x. No abstract available.
Bartelink IH, Bredius RG, Belitser SV, Suttorp MM, Bierings M, Knibbe CA, Egeler M, Lankester AC, Egberts AC, Zwaveling J, Boelens JJ. Association between busulfan exposure and outcome in children receiving intravenous busulfan before hematologic stem cell transplantation. Biol Blood Marrow Transplant. 2009 Feb;15(2):231-41. doi: 10.1016/j.bbmt.2008.11.022.
Bartelink IH, Bredius RG, Ververs TT, Raphael MF, van Kesteren C, Bierings M, Rademaker CM, den Hartigh J, Uiterwaal CS, Zwaveling J, Boelens JJ. Once-daily intravenous busulfan with therapeutic drug monitoring compared to conventional oral busulfan improves survival and engraftment in children undergoing allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2008 Jan;14(1):88-98. doi: 10.1016/j.bbmt.2007.09.015.
Basara N, Baurmann H, Kolbe K, Yaman A, Labopin M, Burchardt A, Huber C, Fauser AA, Schwerdtfeger R. Antithymocyte globulin for the prevention of graft-versus-host disease after unrelated hematopoietic stem cell transplantation for acute myeloid leukemia: results from the multicenter German cooperative study group. Bone Marrow Transplant. 2005 May;35(10):1011-8. doi: 10.1038/sj.bmt.1704957.
Bernardo ME, Zecca M, Piras E, Vacca A, Giorgiani G, Cugno C, Caocci G, Comoli P, Mastronuzzi A, Merli P, La Nasa G, Locatelli F. Treosulfan-based conditioning regimen for allogeneic haematopoietic stem cell transplantation in patients with thalassaemia major. Br J Haematol. 2008 Nov;143(4):548-51. doi: 10.1111/j.1365-2141.2008.07385.x.
Bernaudin F, Socie G, Kuentz M, Chevret S, Duval M, Bertrand Y, Vannier JP, Yakouben K, Thuret I, Bordigoni P, Fischer A, Lutz P, Stephan JL, Dhedin N, Plouvier E, Margueritte G, Bories D, Verlhac S, Esperou H, Coic L, Vernant JP, Gluckman E; SFGM-TC. Long-term results of related myeloablative stem-cell transplantation to cure sickle cell disease. Blood. 2007 Oct 1;110(7):2749-56. doi: 10.1182/blood-2007-03-079665. Epub 2007 Jul 2.
Chiesa R, Cappelli B, Crocchiolo R, Frugnoli I, Biral E, Noe A, Evangelio C, Fossati M, Roccia T, Biffi A, Finizio V, Aiuti A, Broglia M, Bartoli A, Ciceri F, Roncarolo MG, Marktel S. Unpredictability of intravenous busulfan pharmacokinetics in children undergoing hematopoietic stem cell transplantation for advanced beta thalassemia: limited toxicity with a dose-adjustment policy. Biol Blood Marrow Transplant. 2010 May;16(5):622-8. doi: 10.1016/j.bbmt.2009.11.024. Epub 2009 Dec 4.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
2011-004730-34
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
OPBG_361.11
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.