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The University of Southampton
Southampton Clinical Trials Unit

ACCEPT

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

Contact Information:

Email: [email protected]

SAE Reporting:

Email: [email protected]

Essential Trial Documents

ACCEPT - SCTU Contacts 09 Dec 2020

ACCEPT - GP letter v1 26-Oct-2016

ACCEPT - Informed Consent Form Phase II v5 15-Jul-2019

ACCEPT - Informed Consent Form Tissue Block Consent v1 31-May-2018

ACCEPT - Pregnancy Informed Consent Form v3 15-July-2019

ACCEPT - Patient Diary - Continuation Phase for Dose Expansion v2 27-Apr-2018

ACCEPT - Patient Diary - Dose Expansion v2 27-Apr-2018

ACCEPT - Patient Information Card v1 20-May-2017

ACCEPT - Patient Information Sheet Phase II v5 - 15-Jul-2019

ACCEPT - Pregnancy Patient Information Sheet v3 15-Jul-2019

ACCEPT - Patient Information Sheet Tissue Block Screening v1 31-May-2018

ACCEPT - Patient Registration Form v8 02Oct2019.pdf

ACCEPT - Protocol v7 29-OCT-2020

Investigator Site File

ACCEPT - Investigator Site File Index v11 13-Dec-2016

ACCEPT - Study Contacts and Information Page v9 04-Feb-2016

ACCEPT - IB Acknowledgement Receipt v1.0 13-Mar-2017

ACCEPT - Master Patient List v1 16-Jan-2017

ACCEPT Screening Log - v2 29-Aug-2019.pdf

ACCEPT - Site Delegation Log v1 16-Jan-2017

ACCEPT - Site Visit Log v1 14-Feb-2017

ACCEPT - eCRF Completion Guidelines for Sites v2.0 12-Jul-2018

ACCEPT - Principal Investigator Protocol Acknowledgment Page - Version 6.pdf

Lab file

ACCEPT - HMDS Blood Samples Dispatch Log v1 14-Feb-2017

ACCEPT - HMDS Tissue Samples Dispatch Log v1 14-Feb-2017

ACCEPT - HMDS Instructions for collection of Blood Samples and Biopsies v1 14-Feb-2017

ACCEPT HMDS Shipment Form v3 10-Sep-19.pdf

ACCEPT - Lab File Index v1 08-Mar-2017

ACCEPT PD Sample Shipment Form v2 10 Sep 2019.pdf

ACCEPT Pharmacodynamic Manual V3 10 Sep 2019.pdf

ACCEPT Pharmacokinetic Manual V2 15 Oct 2019.pdf

ACCEPT - PK Sample Shipment Form v1.0 19-Aug-2016

ACCEPT - PK Samples Storage Log v1 14-Feb-2017

ACCEPT - WISH Lab Manual v2 23-Oct-2019.pdf

ACCEPT - WISH Sample Worksheet V2.pdf

ACCEPT - DHL Same Day Nederland acerta instruction TempTale version v1 16-March-2017

Pharmacy Documents

ACCEPT - Acalabrutinib Accountability Log v1 10-Feb-2017

ACCEPT - Acalabrutinib Dispensing Log v1 10-Feb-2017

ACCEPT - Drug Order Form v5 03-Feb-2020

ACCEPT - Pharmacy Manual Phase Ib II v2 17-03-2017

SAE Documents

ACCEPT Phase II SAE SUSAR Report Form v2 10-OCT-2019.pdf

Acalabrutinib Investigator Brochure - Edition 8.pdf

Investigator Brochure RCHOP v2 06-Jan-2017

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

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