Risk and response adapted therapy following autologous stem cell transplant in patients with newly diagnosed multiple myeloma (RADAR (UK-MRA Myeloma XV Trial): study protocol for a phase II/III randomised controlled trial.
Creators: name: Royle, Kara-Louise
name: Coulson, Amy Beth
name: Ramasamy, Karthik
name: Cairns, David A
name: Hockaday, Anna
name: Quezada, Sergio
name: Drayson, Mark
name: Kaiser, Martin
name: Owen, Roger
name: Auner, Holger W
name: Cook, Gordon
name: Meads, David
name: Olivier, Catherine
name: Barnard, Lorna
name: Lambkin, Rhiannon
name: Paterson, Andrea
name: Dawkins, Bryony
name: Chapman, Mike
name: Pratt, Guy
name: Popat, Rakesh
name: Jackson, Graham
name: Bygrave, Ceri
name: Sive, Jonathan
name: De Tute, Ruth
name: Chantry, Andrew
name: Parrish, Christopher
name: Cook, Mark
name: Asher, Samir
name: Yong, Kwee
Publisher: name: Apollo - University of Cambridge Repository
Year: 2022
Subjects: Oncology
1506
1717
Myeloma
Clinical trials
Cancer genetics
STATISTICS &amp; RESEARCH METHODS
Protocols &amp; guidelines

description: Peer reviewed: True
description: INTRODUCTION: Multiple myeloma is a plasma cell malignancy that accounts for 1%-2% of newly diagnosed cancers.At diagnosis, approximately 20% of patients can be identified, using cytogenetics, to have inferior survival (high-risk). Additionally, standard-risk patients, with detectable disease (minimal residual disease (MRD)-positive) postautologus stem cell transplant (ASCT), fare worse compared with those who do not (MRD-negative). Research is required to determine whether a risk-adapted approach post-ASCT could further improve patient outcomes. METHODS: RADAR is a UK, multicentre, risk-adapted, response-guided, open-label, randomised controlled trial for transplant-eligible newly diagnosed multiple myeloma patients, using combinations of lenalidomide (R), cyclophosphamide (Cy), bortezomib (Bor), dexamethasone (D) and isatuximab (Isa).Participants receive RCyBorD(x4) induction therapy, followed by high-dose melphalan and ASCT. Post-ASCT, there are three pathways as follows:A phase III discontinuation design to assess de-escalating therapy in standard-risk MRD-negative patients. Participants receive 12 cycles of Isa maintenance. Those who remain MRD-negative are randomised to either continue or stop treatment.A phase II/III multiarm multistage design to test treatment strategies for treatment escalation in standard-risk MRD-positive patients. Participants are randomised to either; R, RBorD(x4) +R, RIsa, or RBorIsaD(x4) + RIsa.A phase II design to assess the activity of intensive treatment strategies in high-risk patients. Participants are randomised to RBorD(x4) +R or RBorIsaD(x4) + RIsa.1400 participants will be registered to allow for 500, 450 and 172 participants in each pathway. Randomisations are equal and treatment is given until disease progression or intolerance. ETHICS AND DISSEMINATION: Ethical approval was granted by the London-Central Research Ethics Committee (20/LO/0238) and capacity and capability confirmed by the appropriate local research and development department for each participating centre prior to opening recruitment. Participant informed consent is required before trial registration and reconfirmed post-ASCT. Results will be disseminated by conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: ISCRTN46841867.