Frailty-adjusted therapy in Transplant Non-Eligible patients with newly diagnosed Multiple Myeloma (FiTNEss (UK-MRA Myeloma XIV Trial)): a study protocol for a randomised phase III trial
Introduction Multiple myeloma is a bone marrow cancer, which predominantly affects older people. The incidence is increasing in an ageing population.Over the last 10 years, patient outcomes have improved. However, this is less apparent in older, less fit patients, who are ineligible for stem cell tr...
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BMJ Publishing Group
2022-06-01
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| author | Roger Owen John Jones David Meads David A Cairns Christopher Parrish Gordon Cook Neil Rabin Matthew Jenner Martin Kaiser Kevin Boyd Graham Jackson Catherine Olivier Amy Beth Coulson Kara-Louise Royle Charlotte Pawlyn Anna Hockaday Jennifer Bird Stella Bowcock Ruth de Tute Hayley Gardner Bryony Dawkins Rowena Henderson Phillip Best Bhuvan Kishore Mark Drayson |
| author_facet | Roger Owen John Jones David Meads David A Cairns Christopher Parrish Gordon Cook Neil Rabin Matthew Jenner Martin Kaiser Kevin Boyd Graham Jackson Catherine Olivier Amy Beth Coulson Kara-Louise Royle Charlotte Pawlyn Anna Hockaday Jennifer Bird Stella Bowcock Ruth de Tute Hayley Gardner Bryony Dawkins Rowena Henderson Phillip Best Bhuvan Kishore Mark Drayson |
| author_sort | Roger Owen |
| collection | DOAJ |
| description | Introduction Multiple myeloma is a bone marrow cancer, which predominantly affects older people. The incidence is increasing in an ageing population.Over the last 10 years, patient outcomes have improved. However, this is less apparent in older, less fit patients, who are ineligible for stem cell transplant. Research is required in this patient group, taking into account frailty and aiming to improve: treatment tolerability, clinical outcomes and quality of life.Methods and analysis Frailty-adjusted therapy in Transplant Non-Eligible patients with newly diagnosed Multiple Myeloma is a national, phase III, multicentre, randomised controlled trial comparing standard (reactive) and frailty-adjusted (adaptive) induction therapy delivery with ixazomib, lenalidomide and dexamethasone (IRD), and to compare maintenance lenalidomide to lenalidomide+ixazomib, in patients with newly diagnosed multiple myeloma not suitable for stem cell transplant. Overall, 740 participants will be registered into the trial to allow 720 and 478 to be randomised at induction and maintenance, respectively.All participants will receive IRD induction with the dosing strategy randomised (1:1) at trial entry. Patients randomised to the standard, reactive arm will commence at the full dose followed by toxicity dependent reactive modifications. Patients randomised to the adaptive arm will commence at a dose level determined by their International Myeloma Working Group frailty score. Following 12 cycles of induction treatment, participants alive and progression free will undergo a second (double-blind) randomisation on a 1:1 basis to maintenance treatment with lenalidomide+placebo versus lenalidomide+ixazomib until disease progression or intolerance.Ethics and dissemination Ethical approval has been obtained from the North East—Tyne & Wear South Research Ethics Committee (19/NE/0125) and capacity and capability confirmed by local research and development departments for each participating centre prior to opening to recruitment. Participants are required to provide written informed consent prior to trial registration. Trial results will be disseminated by conference presentations and peer-reviewed publications.Trial registration number ISRCTN17973108, NCT03720041. |
| format | Article |
| id | doaj-art-3d2818c0a21d4f5daf3843685e054b9c |
| institution | Kabale University |
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| language | English |
| publishDate | 2022-06-01 |
| publisher | BMJ Publishing Group |
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| spelling | doaj-art-3d2818c0a21d4f5daf3843685e054b9c2025-02-01T14:20:10ZengBMJ Publishing GroupBMJ Open2044-60552022-06-0112610.1136/bmjopen-2021-056147Frailty-adjusted therapy in Transplant Non-Eligible patients with newly diagnosed Multiple Myeloma (FiTNEss (UK-MRA Myeloma XIV Trial)): a study protocol for a randomised phase III trialRoger Owen0John Jones1David Meads2David A Cairns3Christopher Parrish4Gordon Cook5Neil Rabin6Matthew Jenner7Martin Kaiser8Kevin Boyd9Graham Jackson10Catherine Olivier11Amy Beth Coulson12Kara-Louise Royle13Charlotte Pawlyn14Anna Hockaday15Jennifer Bird16Stella Bowcock17Ruth de Tute18Hayley Gardner19Bryony Dawkins20Rowena Henderson21Phillip Best22Bhuvan Kishore23Mark Drayson24Haematology Malignancy Diagnostic Service (HMDS), St James`s University Hospital, Leeds, West Yorkshire, UKKing`s College Hospital, London, UK5 Institute of Health Sciences, University of Leeds, Leeds, UKLeeds Cancer Research UK Clinical Trials Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UKDepartment of Haematology, Leeds Teaching Hospitals NHS Trust, Leeds, UKHaematology, Leeds Teaching Hospitals NHS Trust, Leeds, UKDepartment of Haematology, University College London Hospitals NHS Foundation Trust, London, UKDepartment of Haematology, Southampton General Hospital, Southampton, UKThe Department of Haemato-oncology, Royal Marsden Hospital NHS Trust, London, UKDepartment of Haematology, The Royal Marsden Hospital NHS Trust, London, UKDepartment of Haematology, Newcastle University, Newcastle upon Tyne, Tyne and Wear, UKLeeds Institute of Clinical Trials Research, University of Leeds Clinical Trials Research Unit, Leeds, West Yorkshire, UKLeeds Institute of Clinical Trials Research, University of Leeds Clinical Trials Research Unit, Leeds, West Yorkshire, UKLeeds Institute of Clinical Trials Research, University of Leeds Clinical Trials Research Unit, Leeds, West Yorkshire, UKCancer Research UK London Research Institute, London, UKLeeds Institute of Clinical Trials Research, University of Leeds Clinical Trials Research Unit, Leeds, West Yorkshire, UKThames Hospice, Maidenhead, UKDepartment of Haematology, Kings College Hospital NHS Foundation Trust, Princess Royal Hospital, Hull, UKHaematological Malignancy Diagnostic Service (HMDS), Leeds Teaching Hospitals NHS Trust, Leeds, UKDepartment of Haematology and Stem Cell Transplantation, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK6 Academic Unit of Health Economics, Leeds Institute of Health Sciences, University of Leeds, Leeds, UKLeeds Institute of Clinical Trials Research, University of Leeds Clinical Trials Research Unit, Leeds, West Yorkshire, UKLeeds Institute of Clinical Trials Research, University of Leeds Clinical Trials Research Unit, Leeds, West Yorkshire, UKDepartment of Haematology and Stem Cell Transplantation, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UKInstitute of Immunology and Immunotherapy, Department of Haematology, University of Birmingham, Birmingham, UKIntroduction Multiple myeloma is a bone marrow cancer, which predominantly affects older people. The incidence is increasing in an ageing population.Over the last 10 years, patient outcomes have improved. However, this is less apparent in older, less fit patients, who are ineligible for stem cell transplant. Research is required in this patient group, taking into account frailty and aiming to improve: treatment tolerability, clinical outcomes and quality of life.Methods and analysis Frailty-adjusted therapy in Transplant Non-Eligible patients with newly diagnosed Multiple Myeloma is a national, phase III, multicentre, randomised controlled trial comparing standard (reactive) and frailty-adjusted (adaptive) induction therapy delivery with ixazomib, lenalidomide and dexamethasone (IRD), and to compare maintenance lenalidomide to lenalidomide+ixazomib, in patients with newly diagnosed multiple myeloma not suitable for stem cell transplant. Overall, 740 participants will be registered into the trial to allow 720 and 478 to be randomised at induction and maintenance, respectively.All participants will receive IRD induction with the dosing strategy randomised (1:1) at trial entry. Patients randomised to the standard, reactive arm will commence at the full dose followed by toxicity dependent reactive modifications. Patients randomised to the adaptive arm will commence at a dose level determined by their International Myeloma Working Group frailty score. Following 12 cycles of induction treatment, participants alive and progression free will undergo a second (double-blind) randomisation on a 1:1 basis to maintenance treatment with lenalidomide+placebo versus lenalidomide+ixazomib until disease progression or intolerance.Ethics and dissemination Ethical approval has been obtained from the North East—Tyne & Wear South Research Ethics Committee (19/NE/0125) and capacity and capability confirmed by local research and development departments for each participating centre prior to opening to recruitment. Participants are required to provide written informed consent prior to trial registration. Trial results will be disseminated by conference presentations and peer-reviewed publications.Trial registration number ISRCTN17973108, NCT03720041.https://bmjopen.bmj.com/content/12/6/e056147.full |
| spellingShingle | Roger Owen John Jones David Meads David A Cairns Christopher Parrish Gordon Cook Neil Rabin Matthew Jenner Martin Kaiser Kevin Boyd Graham Jackson Catherine Olivier Amy Beth Coulson Kara-Louise Royle Charlotte Pawlyn Anna Hockaday Jennifer Bird Stella Bowcock Ruth de Tute Hayley Gardner Bryony Dawkins Rowena Henderson Phillip Best Bhuvan Kishore Mark Drayson Frailty-adjusted therapy in Transplant Non-Eligible patients with newly diagnosed Multiple Myeloma (FiTNEss (UK-MRA Myeloma XIV Trial)): a study protocol for a randomised phase III trial BMJ Open |
| title | Frailty-adjusted therapy in Transplant Non-Eligible patients with newly diagnosed Multiple Myeloma (FiTNEss (UK-MRA Myeloma XIV Trial)): a study protocol for a randomised phase III trial |
| title_full | Frailty-adjusted therapy in Transplant Non-Eligible patients with newly diagnosed Multiple Myeloma (FiTNEss (UK-MRA Myeloma XIV Trial)): a study protocol for a randomised phase III trial |
| title_fullStr | Frailty-adjusted therapy in Transplant Non-Eligible patients with newly diagnosed Multiple Myeloma (FiTNEss (UK-MRA Myeloma XIV Trial)): a study protocol for a randomised phase III trial |
| title_full_unstemmed | Frailty-adjusted therapy in Transplant Non-Eligible patients with newly diagnosed Multiple Myeloma (FiTNEss (UK-MRA Myeloma XIV Trial)): a study protocol for a randomised phase III trial |
| title_short | Frailty-adjusted therapy in Transplant Non-Eligible patients with newly diagnosed Multiple Myeloma (FiTNEss (UK-MRA Myeloma XIV Trial)): a study protocol for a randomised phase III trial |
| title_sort | frailty adjusted therapy in transplant non eligible patients with newly diagnosed multiple myeloma fitness uk mra myeloma xiv trial a study protocol for a randomised phase iii trial |
| url | https://bmjopen.bmj.com/content/12/6/e056147.full |
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