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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

Phase II open to recruitment

Population

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

Trial Team:

Senior Trial Manager:

Josh Caddy (023 8120 5537)

Trial Manager:

Katy Mercer (023 8120 3509)

Clinical Data Coordinator:

Peter Navin (023 8120 5321)

Contact Information:

Email: accept@soton.ac.uk

Fax: 0844 7740621

SAE Reporting: ctu@soton.ac.uk or 0844 7740621

Essential Trial Documents

ACCEPT - SCTU Contacts 26-Jan-2018

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 v6 15-Jul-2019

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 v4 09-May-2019

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

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