Clinical trial · Interventional
T&B Depletion Non Malignant
A Phase II Multicentre, Randomized, Controlled Open-label Study on the Use of Anti-thymocyte Globulin and Rituximab for Immunomodulation of Graft-versus-host Disease in Allogeneic Matched Transplants for Non Malignancies
NCT01810926CI-TRIAL-00009725unknownPhase 2ClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
• The primary aim of the present trial is to assess in a randomized fashion the benefit on standard graft-versus-host disease (GVHD) prophylaxis of the addition of ATG-Fresenius S ® in transplants from matched related donors (MRD) and of anti-CD20 rituximab in transplants from matched unrelated donors (MUD). Both safety and efficacy of the treatment will be assessed, in particular in respect to the clinical status of the patient, i.e. prevention of graft failure and chronic GvHD and of Ebstein Barr virus (EBV) viremia for MUD patients. 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.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Graft Versus Host Disease | — | UNRESOLVED | — |
Interventions
Interventions (7)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Cyclosporine A | Drug | — | UNRESOLVED |
| Fludarabine | Drug | Fludarabine | ALIAS |
| Methotrexate | Drug | Methotrexate | ALIAS |
| polyclonal antibody | Biological | — | UNRESOLVED |
| Rituximab | Drug | Rituximab | ALIAS |
| Thiotepa | Drug | Thiotepa | ALIAS |
| Treosulfan | Drug | Treosulfan | ALIAS |
Design
Arms and outcomes
Arms (4)
- type
- EXPERIMENTAL
- label
- MRD-Regimen&Polyclonal antibody
- description
- 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
- interventionNames
- Biological: polyclonal antibody
- Drug: Treosulfan
- Drug: Fludarabine
- Drug: Thiotepa
- Drug: Cyclosporine A
- Drug: Methotrexate
- type
- SHAM_COMPARATOR
- label
- MRD-Regimen
- description
- 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
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 28 Days
- Maximum age
- 64 Years
Show eligibility criteria text
Inclusion Criteria: * non malignant haematological and inherited metabolic disorders benefiting from an allogeneic HSCT conditioned with a myeloablative regimen * 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: * Any malignancy * 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
References
Publications (9)
- BACKGROUNDBacigalupo 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. PMID 16635791
- BACKGROUNDBacigalupo 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. PMID 11698275
- BACKGROUNDBallet 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. PMID 73050
- BACKGROUNDBartelink 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. PMID 19167683
- BACKGROUNDBartelink 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. PMID 18158965
- 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.