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Chemotherapy plus Ofatumumab at Standard or Mega dose in relapsed CLL (COSMIC) trial: study protocol for a phase II randomised controlled trial

BACKGROUND: Chronic lymphocytic leukaemia (CLL) is the most common adult leukaemia. Combination immunochemotherapy such as fludarabine, cyclophosphamide and rituximab is the standard first line therapy in fit patients, but there is limited evidence regarding the optimal treatment of patients after r...

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Autores principales: Howard, Dena R., Munir, Talha, Hockaday, Anna, Rawstron, Andy C., Collett, Laura, Oughton, Jamie B., Allsup, David, Bloor, Adrian, Phillips, David, Hillmen, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5028943/
https://www.ncbi.nlm.nih.gov/pubmed/27645620
http://dx.doi.org/10.1186/s13063-016-1581-0
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author Howard, Dena R.
Munir, Talha
Hockaday, Anna
Rawstron, Andy C.
Collett, Laura
Oughton, Jamie B.
Allsup, David
Bloor, Adrian
Phillips, David
Hillmen, Peter
author_facet Howard, Dena R.
Munir, Talha
Hockaday, Anna
Rawstron, Andy C.
Collett, Laura
Oughton, Jamie B.
Allsup, David
Bloor, Adrian
Phillips, David
Hillmen, Peter
author_sort Howard, Dena R.
collection PubMed
description BACKGROUND: Chronic lymphocytic leukaemia (CLL) is the most common adult leukaemia. Combination immunochemotherapy such as fludarabine, cyclophosphamide and rituximab is the standard first line therapy in fit patients, but there is limited evidence regarding the optimal treatment of patients after relapse. Ofatumumab as monotherapy has been proven to be effective in the treatment of relapsed, refractory CLL, and as it is not myelotoxic, it is an ideal drug to combine with chemotherapy. However, the optimal dose of ofatumumab in this setting is not known. The Chemotherapy plus Ofatumumab at Standard or Mega dose in relapsed CLL (COSMIC) trial will assess the efficacy and safety of standard and high (mega) doses of ofatumumab combined with bendamustine or a combination of fludarabine and cyclophosphamide to determine which, if either, schedule should progress to a phase III trial. METHODS/DESIGN: COSMIC is a phase II, multi-centre, randomised, open, parallel group trial for patients with relapsed CLL who are not refractory to fludarabine-based chemotherapy. Participants will be randomised to receive either standard dose or mega dose ofatumumab. Both doses will be given in combination with either bendamustine or fludarabine and cyclophosphamide chemotherapy backbone. The primary objective is to assess the proportion of participants achieving a complete remission following therapy with the two treatment arms (mega versus standard), as assessed at 3 months post treatment. The treatment groups will be assessed independently to determine whether the level of response is acceptable in relation to pre-specified criteria. If both treatment groups show an acceptable level of response, selection criteria will be used to determine which to take forward to a confirmatory phase III trial. A key secondary objective is to assess the dynamics of minimal residual disease (MRD) levels in relapsed disease. Eighty-two participants are planned to be recruited from 18 research centres in the UK. DISCUSSION: Currently there is limited evidence regarding the optimal treatment of patients with relapsed or refractory CLL, and so suitable therapies are urgently needed. The COSMIC trial will identify whether ofatumumab given in combination with chemotherapy is safe and effective in this population, and will identify the optimal doses for further investigation. TRIAL REGISTRATION: ISRCTN51382468. Registered on 21 September 2011. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-016-1581-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-50289432016-09-22 Chemotherapy plus Ofatumumab at Standard or Mega dose in relapsed CLL (COSMIC) trial: study protocol for a phase II randomised controlled trial Howard, Dena R. Munir, Talha Hockaday, Anna Rawstron, Andy C. Collett, Laura Oughton, Jamie B. Allsup, David Bloor, Adrian Phillips, David Hillmen, Peter Trials Study Protocol BACKGROUND: Chronic lymphocytic leukaemia (CLL) is the most common adult leukaemia. Combination immunochemotherapy such as fludarabine, cyclophosphamide and rituximab is the standard first line therapy in fit patients, but there is limited evidence regarding the optimal treatment of patients after relapse. Ofatumumab as monotherapy has been proven to be effective in the treatment of relapsed, refractory CLL, and as it is not myelotoxic, it is an ideal drug to combine with chemotherapy. However, the optimal dose of ofatumumab in this setting is not known. The Chemotherapy plus Ofatumumab at Standard or Mega dose in relapsed CLL (COSMIC) trial will assess the efficacy and safety of standard and high (mega) doses of ofatumumab combined with bendamustine or a combination of fludarabine and cyclophosphamide to determine which, if either, schedule should progress to a phase III trial. METHODS/DESIGN: COSMIC is a phase II, multi-centre, randomised, open, parallel group trial for patients with relapsed CLL who are not refractory to fludarabine-based chemotherapy. Participants will be randomised to receive either standard dose or mega dose ofatumumab. Both doses will be given in combination with either bendamustine or fludarabine and cyclophosphamide chemotherapy backbone. The primary objective is to assess the proportion of participants achieving a complete remission following therapy with the two treatment arms (mega versus standard), as assessed at 3 months post treatment. The treatment groups will be assessed independently to determine whether the level of response is acceptable in relation to pre-specified criteria. If both treatment groups show an acceptable level of response, selection criteria will be used to determine which to take forward to a confirmatory phase III trial. A key secondary objective is to assess the dynamics of minimal residual disease (MRD) levels in relapsed disease. Eighty-two participants are planned to be recruited from 18 research centres in the UK. DISCUSSION: Currently there is limited evidence regarding the optimal treatment of patients with relapsed or refractory CLL, and so suitable therapies are urgently needed. The COSMIC trial will identify whether ofatumumab given in combination with chemotherapy is safe and effective in this population, and will identify the optimal doses for further investigation. TRIAL REGISTRATION: ISRCTN51382468. Registered on 21 September 2011. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-016-1581-0) contains supplementary material, which is available to authorized users. BioMed Central 2016-09-20 /pmc/articles/PMC5028943/ /pubmed/27645620 http://dx.doi.org/10.1186/s13063-016-1581-0 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Study Protocol
Howard, Dena R.
Munir, Talha
Hockaday, Anna
Rawstron, Andy C.
Collett, Laura
Oughton, Jamie B.
Allsup, David
Bloor, Adrian
Phillips, David
Hillmen, Peter
Chemotherapy plus Ofatumumab at Standard or Mega dose in relapsed CLL (COSMIC) trial: study protocol for a phase II randomised controlled trial
title Chemotherapy plus Ofatumumab at Standard or Mega dose in relapsed CLL (COSMIC) trial: study protocol for a phase II randomised controlled trial
title_full Chemotherapy plus Ofatumumab at Standard or Mega dose in relapsed CLL (COSMIC) trial: study protocol for a phase II randomised controlled trial
title_fullStr Chemotherapy plus Ofatumumab at Standard or Mega dose in relapsed CLL (COSMIC) trial: study protocol for a phase II randomised controlled trial
title_full_unstemmed Chemotherapy plus Ofatumumab at Standard or Mega dose in relapsed CLL (COSMIC) trial: study protocol for a phase II randomised controlled trial
title_short Chemotherapy plus Ofatumumab at Standard or Mega dose in relapsed CLL (COSMIC) trial: study protocol for a phase II randomised controlled trial
title_sort chemotherapy plus ofatumumab at standard or mega dose in relapsed cll (cosmic) trial: study protocol for a phase ii randomised controlled trial
topic Study Protocol
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5028943/
https://www.ncbi.nlm.nih.gov/pubmed/27645620
http://dx.doi.org/10.1186/s13063-016-1581-0
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