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
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
Affiliations
Roger Owen
Haematology Malignancy Diagnostic Service (HMDS), St James`s University Hospital, Leeds, West Yorkshire, UK
John Jones
King`s College Hospital, London, UK
David Meads
5 Institute of Health Sciences, University of Leeds, Leeds, UK
David A Cairns
Leeds Cancer Research UK Clinical Trials Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK
Christopher Parrish
Department of Haematology, Leeds Teaching Hospitals NHS Trust, Leeds, UK
Gordon Cook
Haematology, Leeds Teaching Hospitals NHS Trust, Leeds, UK
Neil Rabin
Department of Haematology, University College London Hospitals NHS Foundation Trust, London, UK
Matthew Jenner
Department of Haematology, Southampton General Hospital, Southampton, UK
Martin Kaiser
The Department of Haemato-oncology, Royal Marsden Hospital NHS Trust, London, UK
Kevin Boyd
Department of Haematology, The Royal Marsden Hospital NHS Trust, London, UK
Graham Jackson
Department of Haematology, Newcastle University, Newcastle upon Tyne, Tyne and Wear, UK
Catherine Olivier
Leeds Institute of Clinical Trials Research, University of Leeds Clinical Trials Research Unit, Leeds, West Yorkshire, UK
Amy Beth Coulson
Leeds Institute of Clinical Trials Research, University of Leeds Clinical Trials Research Unit, Leeds, West Yorkshire, UK
Kara-Louise Royle
Leeds Institute of Clinical Trials Research, University of Leeds Clinical Trials Research Unit, Leeds, West Yorkshire, UK
Charlotte Pawlyn
Cancer Research UK London Research Institute, London, UK
Anna Hockaday
Leeds Institute of Clinical Trials Research, University of Leeds Clinical Trials Research Unit, Leeds, West Yorkshire, UK
Jennifer Bird
Thames Hospice, Maidenhead, UK
Stella Bowcock
Department of Haematology, Kings College Hospital NHS Foundation Trust, Princess Royal Hospital, Hull, UK
Ruth de Tute
Haematological Malignancy Diagnostic Service (HMDS), Leeds Teaching Hospitals NHS Trust, Leeds, UK
Hayley Gardner
Department of Haematology and Stem Cell Transplantation, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
Bryony Dawkins
6 Academic Unit of Health Economics, Leeds Institute of Health Sciences, University of Leeds, Leeds, UK
Rowena Henderson
Leeds Institute of Clinical Trials Research, University of Leeds Clinical Trials Research Unit, Leeds, West Yorkshire, UK
Phillip Best
Leeds Institute of Clinical Trials Research, University of Leeds Clinical Trials Research Unit, Leeds, West Yorkshire, UK
Bhuvan Kishore
Department of Haematology and Stem Cell Transplantation, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
Mark Drayson
Institute of Immunology and Immunotherapy, Department of Haematology, University of Birmingham, Birmingham, UK
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.