Cargando…
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
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 (mini...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9677008/ https://www.ncbi.nlm.nih.gov/pubmed/36396306 http://dx.doi.org/10.1136/bmjopen-2022-063037 |
_version_ | 1784833718160982016 |
---|---|
author | Royle, Kara-Louise Coulson, Amy Beth Ramasamy, Karthik Cairns, David A Hockaday, Anna Quezada, Sergio Drayson, Mark Kaiser, Martin Owen, Roger Auner, Holger W Cook, Gordon Meads, David Olivier, Catherine Barnard, Lorna Lambkin, Rhiannon Paterson, Andrea Dawkins, Bryony Chapman, Mike Pratt, Guy Popat, Rakesh Jackson, Graham Bygrave, Ceri Sive, Jonathan de Tute, Ruth Chantry, Andrew Parrish, Christopher Cook, Mark Asher, Samir Yong, Kwee |
author_facet | Royle, Kara-Louise Coulson, Amy Beth Ramasamy, Karthik Cairns, David A Hockaday, Anna Quezada, Sergio Drayson, Mark Kaiser, Martin Owen, Roger Auner, Holger W Cook, Gordon Meads, David Olivier, Catherine Barnard, Lorna Lambkin, Rhiannon Paterson, Andrea Dawkins, Bryony Chapman, Mike Pratt, Guy Popat, Rakesh Jackson, Graham Bygrave, Ceri Sive, Jonathan de Tute, Ruth Chantry, Andrew Parrish, Christopher Cook, Mark Asher, Samir Yong, Kwee |
author_sort | Royle, Kara-Louise |
collection | PubMed |
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: 1. 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. 2. 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. 3. 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. |
format | Online Article Text |
id | pubmed-9677008 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-96770082022-11-22 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 Royle, Kara-Louise Coulson, Amy Beth Ramasamy, Karthik Cairns, David A Hockaday, Anna Quezada, Sergio Drayson, Mark Kaiser, Martin Owen, Roger Auner, Holger W Cook, Gordon Meads, David Olivier, Catherine Barnard, Lorna Lambkin, Rhiannon Paterson, Andrea Dawkins, Bryony Chapman, Mike Pratt, Guy Popat, Rakesh Jackson, Graham Bygrave, Ceri Sive, Jonathan de Tute, Ruth Chantry, Andrew Parrish, Christopher Cook, Mark Asher, Samir Yong, Kwee BMJ Open Oncology 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: 1. 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. 2. 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. 3. 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. BMJ Publishing Group 2022-11-16 /pmc/articles/PMC9677008/ /pubmed/36396306 http://dx.doi.org/10.1136/bmjopen-2022-063037 Text en © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Oncology Royle, Kara-Louise Coulson, Amy Beth Ramasamy, Karthik Cairns, David A Hockaday, Anna Quezada, Sergio Drayson, Mark Kaiser, Martin Owen, Roger Auner, Holger W Cook, Gordon Meads, David Olivier, Catherine Barnard, Lorna Lambkin, Rhiannon Paterson, Andrea Dawkins, Bryony Chapman, Mike Pratt, Guy Popat, Rakesh Jackson, Graham Bygrave, Ceri Sive, Jonathan de Tute, Ruth Chantry, Andrew Parrish, Christopher Cook, Mark Asher, Samir Yong, Kwee 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 |
title | 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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9677008/ https://www.ncbi.nlm.nih.gov/pubmed/36396306 http://dx.doi.org/10.1136/bmjopen-2022-063037 |
work_keys_str_mv | AT roylekaralouise riskandresponseadaptedtherapyfollowingautologousstemcelltransplantinpatientswithnewlydiagnosedmultiplemyelomaradarukmramyelomaxvtrialstudyprotocolforaphaseiiiiirandomisedcontrolledtrial AT coulsonamybeth riskandresponseadaptedtherapyfollowingautologousstemcelltransplantinpatientswithnewlydiagnosedmultiplemyelomaradarukmramyelomaxvtrialstudyprotocolforaphaseiiiiirandomisedcontrolledtrial AT ramasamykarthik riskandresponseadaptedtherapyfollowingautologousstemcelltransplantinpatientswithnewlydiagnosedmultiplemyelomaradarukmramyelomaxvtrialstudyprotocolforaphaseiiiiirandomisedcontrolledtrial AT cairnsdavida riskandresponseadaptedtherapyfollowingautologousstemcelltransplantinpatientswithnewlydiagnosedmultiplemyelomaradarukmramyelomaxvtrialstudyprotocolforaphaseiiiiirandomisedcontrolledtrial AT hockadayanna riskandresponseadaptedtherapyfollowingautologousstemcelltransplantinpatientswithnewlydiagnosedmultiplemyelomaradarukmramyelomaxvtrialstudyprotocolforaphaseiiiiirandomisedcontrolledtrial AT quezadasergio riskandresponseadaptedtherapyfollowingautologousstemcelltransplantinpatientswithnewlydiagnosedmultiplemyelomaradarukmramyelomaxvtrialstudyprotocolforaphaseiiiiirandomisedcontrolledtrial AT draysonmark riskandresponseadaptedtherapyfollowingautologousstemcelltransplantinpatientswithnewlydiagnosedmultiplemyelomaradarukmramyelomaxvtrialstudyprotocolforaphaseiiiiirandomisedcontrolledtrial AT kaisermartin riskandresponseadaptedtherapyfollowingautologousstemcelltransplantinpatientswithnewlydiagnosedmultiplemyelomaradarukmramyelomaxvtrialstudyprotocolforaphaseiiiiirandomisedcontrolledtrial AT owenroger riskandresponseadaptedtherapyfollowingautologousstemcelltransplantinpatientswithnewlydiagnosedmultiplemyelomaradarukmramyelomaxvtrialstudyprotocolforaphaseiiiiirandomisedcontrolledtrial AT aunerholgerw riskandresponseadaptedtherapyfollowingautologousstemcelltransplantinpatientswithnewlydiagnosedmultiplemyelomaradarukmramyelomaxvtrialstudyprotocolforaphaseiiiiirandomisedcontrolledtrial AT cookgordon riskandresponseadaptedtherapyfollowingautologousstemcelltransplantinpatientswithnewlydiagnosedmultiplemyelomaradarukmramyelomaxvtrialstudyprotocolforaphaseiiiiirandomisedcontrolledtrial AT meadsdavid riskandresponseadaptedtherapyfollowingautologousstemcelltransplantinpatientswithnewlydiagnosedmultiplemyelomaradarukmramyelomaxvtrialstudyprotocolforaphaseiiiiirandomisedcontrolledtrial AT oliviercatherine riskandresponseadaptedtherapyfollowingautologousstemcelltransplantinpatientswithnewlydiagnosedmultiplemyelomaradarukmramyelomaxvtrialstudyprotocolforaphaseiiiiirandomisedcontrolledtrial AT barnardlorna riskandresponseadaptedtherapyfollowingautologousstemcelltransplantinpatientswithnewlydiagnosedmultiplemyelomaradarukmramyelomaxvtrialstudyprotocolforaphaseiiiiirandomisedcontrolledtrial AT lambkinrhiannon riskandresponseadaptedtherapyfollowingautologousstemcelltransplantinpatientswithnewlydiagnosedmultiplemyelomaradarukmramyelomaxvtrialstudyprotocolforaphaseiiiiirandomisedcontrolledtrial AT patersonandrea riskandresponseadaptedtherapyfollowingautologousstemcelltransplantinpatientswithnewlydiagnosedmultiplemyelomaradarukmramyelomaxvtrialstudyprotocolforaphaseiiiiirandomisedcontrolledtrial AT dawkinsbryony riskandresponseadaptedtherapyfollowingautologousstemcelltransplantinpatientswithnewlydiagnosedmultiplemyelomaradarukmramyelomaxvtrialstudyprotocolforaphaseiiiiirandomisedcontrolledtrial AT chapmanmike riskandresponseadaptedtherapyfollowingautologousstemcelltransplantinpatientswithnewlydiagnosedmultiplemyelomaradarukmramyelomaxvtrialstudyprotocolforaphaseiiiiirandomisedcontrolledtrial AT prattguy riskandresponseadaptedtherapyfollowingautologousstemcelltransplantinpatientswithnewlydiagnosedmultiplemyelomaradarukmramyelomaxvtrialstudyprotocolforaphaseiiiiirandomisedcontrolledtrial AT popatrakesh riskandresponseadaptedtherapyfollowingautologousstemcelltransplantinpatientswithnewlydiagnosedmultiplemyelomaradarukmramyelomaxvtrialstudyprotocolforaphaseiiiiirandomisedcontrolledtrial AT jacksongraham riskandresponseadaptedtherapyfollowingautologousstemcelltransplantinpatientswithnewlydiagnosedmultiplemyelomaradarukmramyelomaxvtrialstudyprotocolforaphaseiiiiirandomisedcontrolledtrial AT bygraveceri riskandresponseadaptedtherapyfollowingautologousstemcelltransplantinpatientswithnewlydiagnosedmultiplemyelomaradarukmramyelomaxvtrialstudyprotocolforaphaseiiiiirandomisedcontrolledtrial AT sivejonathan riskandresponseadaptedtherapyfollowingautologousstemcelltransplantinpatientswithnewlydiagnosedmultiplemyelomaradarukmramyelomaxvtrialstudyprotocolforaphaseiiiiirandomisedcontrolledtrial AT detuteruth riskandresponseadaptedtherapyfollowingautologousstemcelltransplantinpatientswithnewlydiagnosedmultiplemyelomaradarukmramyelomaxvtrialstudyprotocolforaphaseiiiiirandomisedcontrolledtrial AT chantryandrew riskandresponseadaptedtherapyfollowingautologousstemcelltransplantinpatientswithnewlydiagnosedmultiplemyelomaradarukmramyelomaxvtrialstudyprotocolforaphaseiiiiirandomisedcontrolledtrial AT parrishchristopher riskandresponseadaptedtherapyfollowingautologousstemcelltransplantinpatientswithnewlydiagnosedmultiplemyelomaradarukmramyelomaxvtrialstudyprotocolforaphaseiiiiirandomisedcontrolledtrial AT cookmark riskandresponseadaptedtherapyfollowingautologousstemcelltransplantinpatientswithnewlydiagnosedmultiplemyelomaradarukmramyelomaxvtrialstudyprotocolforaphaseiiiiirandomisedcontrolledtrial AT ashersamir riskandresponseadaptedtherapyfollowingautologousstemcelltransplantinpatientswithnewlydiagnosedmultiplemyelomaradarukmramyelomaxvtrialstudyprotocolforaphaseiiiiirandomisedcontrolledtrial AT yongkwee riskandresponseadaptedtherapyfollowingautologousstemcelltransplantinpatientswithnewlydiagnosedmultiplemyelomaradarukmramyelomaxvtrialstudyprotocolforaphaseiiiiirandomisedcontrolledtrial |