ACCEPT

Trial Overview

Trial Team

Essential Trial Documentation

Publications and Presentations

Title

A Phase Ib/II combination of acalabrutinib with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) for patient Diffuse Large B-cell Lymphoma (DLBCL)

Description

Retrospective molecular profiling of untreated DLBCL samples has recognised 3 distinct sub-classifications of this disease (ABC-DLBCL, GCB- DLBCL and unclassified DLBCL), each with unique biological features and clinical outcomes when treated with CHOP or R-CHOP chemotherapy. Dysregulation of B-cell receptors (BCR) signalling pathway is observed in ABC type and requires Bruton tyrosine kinase (Btk) activation. Clinical studies have shown that targeting BCR signalling pathway by the inhibition of Btk with ibrutinib (a 1st generation Btk inhibitor) in combination with R-CHOP chemotherapy for previously untreated B-cell non Hodgkin lymphoma is safe. Acalabrutinib is a 2nd generation Btk inhibitor with increased target selectivity compared to ibrutinib. It is postulated that the addition of acalabrutinib to R-CHOP chemotherapy may improve tumour response compared to ibrutinib + R-CHOP. ACCEPT is an open-label non-randomised phase Ib/II study conducted in two stages. Stage 1 will be dose escalation in a modified classical 6+6 design. Stage 2 will be an expansion cohort to gain additional information on safety and efficacy at the recommended phase II dose of acalabrutinib.

Objectives

Phase I:

To propose a recommended dose for Phase II evaluation of acalabrutinib in combination with R-CHOP in patients with DLBCL
To examine the safety and toxicity profile of acalabrutinib in combination with R-CHOP and defining the dose limiting toxicity or maximum administered dose

Phase II:

To document anti-tumour activity of acalabrutinib in combination with R-CHOP in patients with previously untreated CD20 positive DLBCL
To determine additional safety information of acalabrutinib in combination with R-CHOP

Trial Design

Open-label non-randomised phase Ib/II study conducted in two stages. Stage 1 will be dose escalation in a modified classical 6+6 design. Stage 2 will be an expansion cohort to gain additional information on safety and efficacy at the recommended phase II dose of acalabrutinib.

Trial Status

In follow-up

Population

Patients with previously untreated CD20 positive diffuse large B-cell lymphoma (DLBCL) requiring full course chemoimmunotherapy.

CRUK logo

This trial is endorsed by Cancer Research UK (award reference no. CRUKDE/16/006)

Trial Team:

Senior Trial Manager:

Katy McLaughlin

Trial Manager:

Chris Wignall

Clinical Data Manager:

Mike Radford

Clinical Data Coordinator:

Robert Waugh

Davies A, et al; Acalabrutinib in Combination with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisolone (R-CHOP) As First Line Therapy for Patients with Diffuse Large B-Cell Lymphoma (DLBCL): The Accept Phase Ib/II Single Arm Study. Blood 2020; 136 (Supplement 1): 38–39. doi: https://doi.org/10.1182/blood-2020-134546

Davies A, et al; Acalabrutinib in Combination with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisolone (R-CHOP) As First Line Therapy for Patients with Diffuse Large B-Cell Lymphoma (DLBCL): The Accept Phase Ib/II Single Arm Study. Poster Presentation at the 62nd American Society of Haematology (ASH) Annual Meeting and Exposition, December 2020, San Diego CA, USA.

Davies A, et al. 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 https://doi.org/10.12688/f1000research.22318.1

Cummin, T., et al. (2019), ACCEPT: A PHASE IB/II COMBINATION OF ACALABRUTINIB WITH RITUXIMAB, CYCLOPHOSPHAMIDE, DOXORUBICIN, VINCRISTINE AND PREDNISOLONE (R-CHOP) FOR PATIENTS WITH DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL). Hematol Oncol, 37: 71-72. https://doi.org/10.1002/hon.39_2629

Cummin, T., et al. (2019), ACCEPT: A PHASE IB/II COMBINATION OF ACALABRUTINIB WITH RITUXIMAB, CYCLOPHOSPHAMIDE, DOXORUBICIN, VINCRISTINE AND PREDNISOLONE (R-CHOP) FOR PATIENTS WITH DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL). Oral presentation at the 15th International Conference on Malignant Lymphoma, May 2019, Lugano Switzerland.

ACCEPT: A phase Ib/II combination of acalabrutinib with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) for patients with diffuse large B-cell lymphoma (DLBCL). Poster presentation at the American Association for Cancer Research Annual Meeting 2018, April 2018, Chicago IL, USA

ACCEPT

Trial Overview

Trial Team

Essential Trial Documentation

Publications and Presentations

Title

Description

Objectives

Trial Design

Trial Status

Population

Trial Team:

Senior Trial Manager:

Trial Manager:

Clinical Data Coordinator:

Contact Information:

SAE Reporting:

Essential Trial Documents

Investigator Site File

Lab file

Pharmacy Documents

SAE Documents