Multicentre adaptive randomised trial of GvHD prophylaxis following unrelated donor stem cell transplantation comparing Thymoglobulin versus calcineurin inhibitor-based or sirolimus-based post-transplant cyclophosphamide (Methods of T cell Depletion, MoTD trial)
Introduction Graft-versus-host disease (GvHD) remains a major complication of allogeneic stem cell transplantation (allo-SCT), affecting 30–70% of patients (representing 800 new patients per year in the UK). The risk is higher in patients undergoing unrelated allo-SCT. About 1 in 10 patients die as...
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2025-01-01
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| Online Access: | https://bmjopen.bmj.com/content/15/1/e086223.full |
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| author | Simon Gates Matthew Collin Victoria Potter Rebecca Bishop Ronjon Chakraverty Kavita Raj Adrian Bloor Andrea Hodgkinson Jeff Davies Emma Kempshall Fiona Dignan Ram Malladi Siobhan Smith Charlotte Gaskell Gabrielle Smith |
| author_facet | Simon Gates Matthew Collin Victoria Potter Rebecca Bishop Ronjon Chakraverty Kavita Raj Adrian Bloor Andrea Hodgkinson Jeff Davies Emma Kempshall Fiona Dignan Ram Malladi Siobhan Smith Charlotte Gaskell Gabrielle Smith |
| author_sort | Simon Gates |
| collection | DOAJ |
| description | Introduction Graft-versus-host disease (GvHD) remains a major complication of allogeneic stem cell transplantation (allo-SCT), affecting 30–70% of patients (representing 800 new patients per year in the UK). The risk is higher in patients undergoing unrelated allo-SCT. About 1 in 10 patients die as a result of GvHD or through complications of its treatment. In patients who survive GvHD and or the complications of treatment, about 1 in 3 patients develop chronic GvHD which has a negative impact on quality of life (QoL). Many transplant protocols use alemtuzumab or anti-thymocyte globulin (ATG) in combination with a calcineurin inhibitor (CNI) and mycophenolate mofetil as GvHD prophylaxis; however, the outcomes of these treatments are complicated by high rates of infection and therefore the development of improved GvHD prophylaxis strategies represents a major unmet need.Methods and analysis The Methods of T-Cell Depletion trial is a prospective, multicentre, adaptive randomised trial in patients undergoing reduced intensity-conditioned unrelated donor allo-SCT. The trial will compare the novel GvHD prophylaxis regimens post-transplant cyclophosphamide (PTCy) in combination with a CNI or sirolimus (PTCy-CNI or PTCy-sirolimus, respectively) to a current standard-of-care GvHD prophylaxis involving the use of Thymoglobulin (a specific brand of ATG containing rabbit polyclonal antibodies). The primary outcome measure is GvHD-free, relapse-free survival at 1 year. Secondary outcomes include cumulative incidence of acute grade II-IV GvHD at 1 year, cumulative incidence of moderate and severe chronic GvHD at 1 year, overall survival at 1 year and cumulative incidence of non-relapse mortality at 1 year.Ethics and dissemination The protocol was approved by the West Midlands, Edgbaston Research Ethics Committee (20/WM/0195); initial approval was received on 11 September 2020, current protocol version (V.4.0) approval on 25 July 2023. The Medicines and Healthcare products Regulatory Authority also approved all protocol versions. The results of this trial will be disseminated through national and international presentations and peer-reviewed publications.Trial registration number EudraCT Number: 2019-002419-24.ISRCTN Number: 50290131. |
| format | Article |
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| institution | Kabale University |
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| spelling | doaj-art-f78ff4db9556481cb626dde49f196f2a2025-01-31T20:15:10ZengBMJ Publishing GroupBMJ Open2044-60552025-01-0115110.1136/bmjopen-2024-086223Multicentre adaptive randomised trial of GvHD prophylaxis following unrelated donor stem cell transplantation comparing Thymoglobulin versus calcineurin inhibitor-based or sirolimus-based post-transplant cyclophosphamide (Methods of T cell Depletion, MoTD trial)Simon Gates0Matthew Collin1Victoria Potter2Rebecca Bishop3Ronjon Chakraverty4Kavita Raj5Adrian Bloor6Andrea Hodgkinson7Jeff Davies8Emma Kempshall9Fiona Dignan10Ram Malladi11Siobhan Smith12Charlotte Gaskell13Gabrielle Smith1412 Clinical Trials Unit, University of Warwick, Coventry, UK5 Department of Haematology, Newcastle Freeman Hospital, High Heaton Newcastle upon Tyne, UK8 Department of Haematology, King’s College London, London, UK11 Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK1 Haematology, Oxford Cancer and Haematology Centre, Oxford, UK6 Department of Haematology, University College London Hospitals NHS Foundation, London, UK4 Haematology, The Christie NHS Foundation Trust, Manchester, UK14 University of Birmingham, Birmingham, UK7 Centre for Haemato-Oncology, Queen Mary University London Charterhouse Square, London, UK2 Department of Haematology, University Hospital of Wales, Cardiff, UK3 Department of Clinical Haematology, Manchester Royal Infirmary, Manchester, UK9 Haematology, Addenbrooke`s Hospital, Cambridge, UK10 Pharmacy, University Hospital of Wales, Cardiff, UK13 Queen Elizabeth Hospital, Birmingham, UK11 Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UKIntroduction Graft-versus-host disease (GvHD) remains a major complication of allogeneic stem cell transplantation (allo-SCT), affecting 30–70% of patients (representing 800 new patients per year in the UK). The risk is higher in patients undergoing unrelated allo-SCT. About 1 in 10 patients die as a result of GvHD or through complications of its treatment. In patients who survive GvHD and or the complications of treatment, about 1 in 3 patients develop chronic GvHD which has a negative impact on quality of life (QoL). Many transplant protocols use alemtuzumab or anti-thymocyte globulin (ATG) in combination with a calcineurin inhibitor (CNI) and mycophenolate mofetil as GvHD prophylaxis; however, the outcomes of these treatments are complicated by high rates of infection and therefore the development of improved GvHD prophylaxis strategies represents a major unmet need.Methods and analysis The Methods of T-Cell Depletion trial is a prospective, multicentre, adaptive randomised trial in patients undergoing reduced intensity-conditioned unrelated donor allo-SCT. The trial will compare the novel GvHD prophylaxis regimens post-transplant cyclophosphamide (PTCy) in combination with a CNI or sirolimus (PTCy-CNI or PTCy-sirolimus, respectively) to a current standard-of-care GvHD prophylaxis involving the use of Thymoglobulin (a specific brand of ATG containing rabbit polyclonal antibodies). The primary outcome measure is GvHD-free, relapse-free survival at 1 year. Secondary outcomes include cumulative incidence of acute grade II-IV GvHD at 1 year, cumulative incidence of moderate and severe chronic GvHD at 1 year, overall survival at 1 year and cumulative incidence of non-relapse mortality at 1 year.Ethics and dissemination The protocol was approved by the West Midlands, Edgbaston Research Ethics Committee (20/WM/0195); initial approval was received on 11 September 2020, current protocol version (V.4.0) approval on 25 July 2023. The Medicines and Healthcare products Regulatory Authority also approved all protocol versions. The results of this trial will be disseminated through national and international presentations and peer-reviewed publications.Trial registration number EudraCT Number: 2019-002419-24.ISRCTN Number: 50290131.https://bmjopen.bmj.com/content/15/1/e086223.full |
| spellingShingle | Simon Gates Matthew Collin Victoria Potter Rebecca Bishop Ronjon Chakraverty Kavita Raj Adrian Bloor Andrea Hodgkinson Jeff Davies Emma Kempshall Fiona Dignan Ram Malladi Siobhan Smith Charlotte Gaskell Gabrielle Smith Multicentre adaptive randomised trial of GvHD prophylaxis following unrelated donor stem cell transplantation comparing Thymoglobulin versus calcineurin inhibitor-based or sirolimus-based post-transplant cyclophosphamide (Methods of T cell Depletion, MoTD trial) BMJ Open |
| title | Multicentre adaptive randomised trial of GvHD prophylaxis following unrelated donor stem cell transplantation comparing Thymoglobulin versus calcineurin inhibitor-based or sirolimus-based post-transplant cyclophosphamide (Methods of T cell Depletion, MoTD trial) |
| title_full | Multicentre adaptive randomised trial of GvHD prophylaxis following unrelated donor stem cell transplantation comparing Thymoglobulin versus calcineurin inhibitor-based or sirolimus-based post-transplant cyclophosphamide (Methods of T cell Depletion, MoTD trial) |
| title_fullStr | Multicentre adaptive randomised trial of GvHD prophylaxis following unrelated donor stem cell transplantation comparing Thymoglobulin versus calcineurin inhibitor-based or sirolimus-based post-transplant cyclophosphamide (Methods of T cell Depletion, MoTD trial) |
| title_full_unstemmed | Multicentre adaptive randomised trial of GvHD prophylaxis following unrelated donor stem cell transplantation comparing Thymoglobulin versus calcineurin inhibitor-based or sirolimus-based post-transplant cyclophosphamide (Methods of T cell Depletion, MoTD trial) |
| title_short | Multicentre adaptive randomised trial of GvHD prophylaxis following unrelated donor stem cell transplantation comparing Thymoglobulin versus calcineurin inhibitor-based or sirolimus-based post-transplant cyclophosphamide (Methods of T cell Depletion, MoTD trial) |
| title_sort | multicentre adaptive randomised trial of gvhd prophylaxis following unrelated donor stem cell transplantation comparing thymoglobulin versus calcineurin inhibitor based or sirolimus based post transplant cyclophosphamide methods of t cell depletion motd trial |
| url | https://bmjopen.bmj.com/content/15/1/e086223.full |
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