ACCEPT - combining acalabrutinib with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) for Diffuse Large B-cell Lymphoma (DLBCL): study protocol for a Phase Ib/II open-label non-randomised clinical trial [version 1; peer review: 2 approved]
Background: Over 13,000 new cases of non-Hodgkin’s lymphoma (NHL) are diagnosed in the UK, with approximately 4,900 attributable deaths each year. Diffuse Large B-cell Lymphoma (DLBCL) is the most common NHL comprising one third of adult NHL cases. R-CHOP (rituximab, cyclophosphamide, doxorubicin, v...
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| Format: | Article |
| Language: | English |
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F1000 Research Ltd
2020-08-01
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| Series: | F1000Research |
| Online Access: | https://f1000research.com/articles/9-941/v1 |
| _version_ | 1818880554558291968 |
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| author | Andrew Davies Sharon Barrans Cathy Burton Katy Mercer Joshua Caddy Fay Chinnery Laura Day Diana Fernando Kirit Ardeshna Graham Collins John Radford Simon Rule Andrew McMillan Peter Johnson Gareth Griffiths |
| author_facet | Andrew Davies Sharon Barrans Cathy Burton Katy Mercer Joshua Caddy Fay Chinnery Laura Day Diana Fernando Kirit Ardeshna Graham Collins John Radford Simon Rule Andrew McMillan Peter Johnson Gareth Griffiths |
| author_sort | Andrew Davies |
| collection | DOAJ |
| description | Background: Over 13,000 new cases of non-Hodgkin’s lymphoma (NHL) are diagnosed in the UK, with approximately 4,900 attributable deaths each year. Diffuse Large B-cell Lymphoma (DLBCL) is the most common NHL comprising one third of adult NHL cases. R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) is accepted as the international standard first-line regimen, but improvement in first line treatment is needed. Dysregulated B-cell receptor (BCR) signalling has been identified as a feature of DLBCL. Inhibition of Bruton’s tyrosine kinase (Btk), downstream of the BCR has proven efficacious in other B-cell malignancies and in combination with R-CHOP. The second generation Btk inhibitor, acalabrutinib, may have improved target potency and specificity, and therefore better efficacy and tolerability. Methods: ACCEPT is an open-label non-randomised Phase Ib/II trial testing the addition of acalabrutinib to conventional R-CHOP therapy. ACCEPT incorporates an initial 6+6 modified Phase I design of up to 24 participants followed by 15 participant single arm Phase II expansion cohort in treatment naive patients with histologically confirmed DLBCL expressing CD20. Participants are recruited from UK secondary care sites. Phase I will establish the recommended Phase II dose (RP2D, primary endpoint) of acalabrutinib in combination with R-CHOP. Phase II will gain additional information on safety and efficacy on the RP2D. The primary endpoints of Phase II are overall response rate and toxicity profile. Secondary endpoints include duration of response (progression-free survival and overall survival OS) in relation to cell of origin. Analyses are not powered for formal statistical comparisons; descriptive statistics will describe rates of toxicity, efficacy and translational endpoints. Discussion: ACCEPT will provide evidence for whether acalabrutinib in combination with R-CHOP is safe and biologically effective prior to future Phase II/III trials in patients with previously untreated CD20 positive DLBCL. Trial registration: EudraCT Number: 2015-003213-18 (issued 16 July 2015); ISRCTN13626902 (registered 07 March 2017). |
| first_indexed | 2024-12-19T14:47:49Z |
| format | Article |
| id | doaj.art-db65a63ed78441e69e7645344810acd2 |
| institution | Directory Open Access Journal |
| issn | 2046-1402 |
| language | English |
| last_indexed | 2024-12-19T14:47:49Z |
| publishDate | 2020-08-01 |
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| series | F1000Research |
| spelling | doaj.art-db65a63ed78441e69e7645344810acd22022-12-21T20:16:55ZengF1000 Research LtdF1000Research2046-14022020-08-01910.12688/f1000research.22318.124618ACCEPT - combining acalabrutinib with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) for Diffuse Large B-cell Lymphoma (DLBCL): study protocol for a Phase Ib/II open-label non-randomised clinical trial [version 1; peer review: 2 approved]Andrew Davies0Sharon Barrans1Cathy Burton2Katy Mercer3Joshua Caddy4Fay Chinnery5Laura Day6Diana Fernando7Kirit Ardeshna8Graham Collins9John Radford10Simon Rule11Andrew McMillan12Peter Johnson13Gareth Griffiths14Southampton Experimental Cancer Medicine Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southhampton, UKLeeds Teaching Hospitals NHS Trust, Leeds, UKLeeds Teaching Hospitals NHS Trust, Leeds, UKSouthampton Clinical Trials Unit, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UKSouthampton Clinical Trials Unit, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UKSouthampton Clinical Trials Unit, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UKSouthampton Clinical Trials Unit, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UKSouthampton Clinical Trials Unit, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UKUniversity College London Hospitals NHS Foundation Trust, London, UKOxford University Hospitals NHS Trust, Oxford, UKUniversity of Manchester, Manchester, UKPlymouth Hospitals NHS Trust and Plymouth University Peninsula School of Medicine and Dentistry, Plymouth, UKNottingham University Hospitals NHS Trust, Nottingham, UKSouthampton Experimental Cancer Medicine Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southhampton, UKSouthampton Clinical Trials Unit, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UKBackground: Over 13,000 new cases of non-Hodgkin’s lymphoma (NHL) are diagnosed in the UK, with approximately 4,900 attributable deaths each year. Diffuse Large B-cell Lymphoma (DLBCL) is the most common NHL comprising one third of adult NHL cases. R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) is accepted as the international standard first-line regimen, but improvement in first line treatment is needed. Dysregulated B-cell receptor (BCR) signalling has been identified as a feature of DLBCL. Inhibition of Bruton’s tyrosine kinase (Btk), downstream of the BCR has proven efficacious in other B-cell malignancies and in combination with R-CHOP. The second generation Btk inhibitor, acalabrutinib, may have improved target potency and specificity, and therefore better efficacy and tolerability. Methods: ACCEPT is an open-label non-randomised Phase Ib/II trial testing the addition of acalabrutinib to conventional R-CHOP therapy. ACCEPT incorporates an initial 6+6 modified Phase I design of up to 24 participants followed by 15 participant single arm Phase II expansion cohort in treatment naive patients with histologically confirmed DLBCL expressing CD20. Participants are recruited from UK secondary care sites. Phase I will establish the recommended Phase II dose (RP2D, primary endpoint) of acalabrutinib in combination with R-CHOP. Phase II will gain additional information on safety and efficacy on the RP2D. The primary endpoints of Phase II are overall response rate and toxicity profile. Secondary endpoints include duration of response (progression-free survival and overall survival OS) in relation to cell of origin. Analyses are not powered for formal statistical comparisons; descriptive statistics will describe rates of toxicity, efficacy and translational endpoints. Discussion: ACCEPT will provide evidence for whether acalabrutinib in combination with R-CHOP is safe and biologically effective prior to future Phase II/III trials in patients with previously untreated CD20 positive DLBCL. Trial registration: EudraCT Number: 2015-003213-18 (issued 16 July 2015); ISRCTN13626902 (registered 07 March 2017).https://f1000research.com/articles/9-941/v1 |
| spellingShingle | Andrew Davies Sharon Barrans Cathy Burton Katy Mercer Joshua Caddy Fay Chinnery Laura Day Diana Fernando Kirit Ardeshna Graham Collins John Radford Simon Rule Andrew McMillan Peter Johnson Gareth Griffiths ACCEPT - combining acalabrutinib with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) for Diffuse Large B-cell Lymphoma (DLBCL): study protocol for a Phase Ib/II open-label non-randomised clinical trial [version 1; peer review: 2 approved] F1000Research |
| title | ACCEPT - combining acalabrutinib with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) for Diffuse Large B-cell Lymphoma (DLBCL): study protocol for a Phase Ib/II open-label non-randomised clinical trial [version 1; peer review: 2 approved] |
| title_full | ACCEPT - combining acalabrutinib with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) for Diffuse Large B-cell Lymphoma (DLBCL): study protocol for a Phase Ib/II open-label non-randomised clinical trial [version 1; peer review: 2 approved] |
| title_fullStr | ACCEPT - combining acalabrutinib with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) for Diffuse Large B-cell Lymphoma (DLBCL): study protocol for a Phase Ib/II open-label non-randomised clinical trial [version 1; peer review: 2 approved] |
| title_full_unstemmed | ACCEPT - combining acalabrutinib with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) for Diffuse Large B-cell Lymphoma (DLBCL): study protocol for a Phase Ib/II open-label non-randomised clinical trial [version 1; peer review: 2 approved] |
| title_short | ACCEPT - combining acalabrutinib with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) for Diffuse Large B-cell Lymphoma (DLBCL): study protocol for a Phase Ib/II open-label non-randomised clinical trial [version 1; peer review: 2 approved] |
| title_sort | accept combining acalabrutinib with rituximab cyclophosphamide doxorubicin vincristine and prednisolone r chop for diffuse large b cell lymphoma dlbcl study protocol for a phase ib ii open label non randomised clinical trial version 1 peer review 2 approved |
| url | https://f1000research.com/articles/9-941/v1 |
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