F railty-adjusted therapy i n T ransplant N on- E ligible patient s with newly diagno s ed Multiple Myeloma (FiTNEss (UK-MRA Myeloma XIV Trial)): a study protocol for a randomised phase III trial
Amy Beth Coulson, Kara-Louise Royle, Charlotte Pawlyn, David A Cairns, Anna Hockaday, Jennifer Bird, Stella Bowcock, Martin Kaiser, Ruth de Tute, Neil Rabin, Kevin Boyd, John Jones, Christopher Parrish, Hayley Gardner, David Meads, Bryony Dawkins, Catherine Olivier, Rowena Henderson, Phillip Best, Roger Owen, Matthew Jenner, Bhuvan Kishore, Mark Drayson, Graham Jackson, Gordon Cook, Amy Beth Coulson, Kara-Louise Royle, Charlotte Pawlyn, David A Cairns, Anna Hockaday, Jennifer Bird, Stella Bowcock, Martin Kaiser, Ruth de Tute, Neil Rabin, Kevin Boyd, John Jones, Christopher Parrish, Hayley Gardner, David Meads, Bryony Dawkins, Catherine Olivier, Rowena Henderson, Phillip Best, Roger Owen, Matthew Jenner, Bhuvan Kishore, Mark Drayson, Graham Jackson, Gordon Cook
Abstract
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.
Keywords: CHEMOTHERAPY; Clinical trials; Myeloma.
Conflict of interest statement
Competing interests: ABC, K-LR, DAC, AH, CO, RH and PB report grants and non-financial support from BMS/Celgene, grants and non-financial support from Merck Sharpe & Dohme, grants and non-financial support from Amgen, grants and non-financial support from Takeda, during the conduct of the trial. DAC also reports travel support from Celgene Corporation. CPawlyn reports receiving honoraria and/or travel support from Amgen, BMS/Celgene, Janssen, Sanofi and Takeda. MK consultancy: AbbVie, Amgen, BMS/Celgene, GSK, Janssen, Karyopharm, Seattle Genetics, Takeda; honoraria: BMS/Celgene, Janssen, Takeda; Research funding: BMS/Celgene; Travel/educational support: BMS/Celgene, Janssen, Takeda. SB reports receiving research funding from Takeda. KB—Advisory Boards Janssen: BMS/Celgene, Takeda, Novartis. Speaker Honoraria: Janssen, BMS/Celgene, Sanofi, Takeda. Support to attend educational meetings: Janssen, BMS/Celgene, Takeda, GSK. GJ reports research funding from Takeda, Onyx, MSD & BMS/Celgene with consultancy from Janssen, Takeda, Sanofi, Oncopeptides, Karyopharm, Pfizer, Roche & BMS/Celgene. GC reports research funding from Janssen, Takeda, Amgen & BMS/Celgene with consultancy from Janssen, Takeda, Sanofi, Oncopeptides, Karyopharm, Pfizer, Roche & BMS/Celgene. MD reports Stock held in Abingdon Health. JB, RdT, NR, JJ, CParrish, HG, DM, BD, RO, MJ and BK have no declared competing interests.
© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.
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