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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.pdf

ACCEPT - GP letter v1 26-Oct-2016.doc

ACCEPT - Informed Consent Form Phase I v4 12-Jan-18.docx

ACCEPT - Patient Information Sheet Phase I - v4 03-Nov-17.pdf

ACCEPT - Patient Information Sheet Pregnant Partner v2 05-07-18.pdf

ACCEPT - Informed Consent Form Tissue Block Consent v1 31-May-18.pdf

ACCEPT - Informed Consent Form Pregnant Partner v2 05-July-18.pdf

ACCEPT - Patient Information Card v1 20-May-17.pdf

ACCEPT - Patient Diary - Cohort 2 - Dose Escalation v2 27 Apr 2018.pdf

ACCEPT - Patient Diary - Continuation Phase Cohort 2 v2 27 Apr 2018.pdf

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

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

ACCEPT - Protocol v5 08 Nov 2018.pdf

Investigator Brochure ACP196 Edition 7-1.pdf

Investigator Brochure RCHOP v2 06-Jan-17.pdf

ACCEPT - Phase II Patient Registration Form v7 23-July-18

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

Phase II trial documents

ACCEPT - Informed Consent Form Phase II v4 31-May-18.pdf

ACCEPT - Patient Diary - Dose Expansion v1 16-Nov-16.pdf

ACCEPT - Patient Information Sheet Phase II - v4 - 31-May-18.pdf

Investigator Site File

ACCEPT - Investigator Site File Index v11 13DEC2016.pdf

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

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

ACCEPT - Master Patient List v1 16-Jan-2017.pdf

ACCEPT - Patient Screening Log v1 14-Feb-2017.pdf

ACCEPT - Site Delegation Log v1 16-Jan-2017.pdf

ACCEPT - Site Visit Log v1 14-Feb-2017.pdf

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

Principal Investigator Protocol Acknowledgment Form - Amendment 4.0.pdf

Lab file

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

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

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

ACCEPT - HMDS Sample Shipment Form v2 19-Apr-2018pdf

ACCEPT - Lab File Index v1 08 MAR2017.pdf

ACCEPT - PD Sample Shipment Form 08 Dec 2016.pdf

ACCEPT - Pharmacodynamic and Lymph Node Manual 19-Oct-2017.pdf

ACCEPT - PK Laboratory Manual v1 19-Aug-16.pdf

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

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

ACCEPT - WISH Lab Manual v1 08 March 2017.pdf

ACCEPT - WISH Lab Sample Form v1 08 March 2017.pdf

Pharmacy Documents

ACCEPT - Acalabrutinib Accountability Log v1 10-Feb-17.pdf

ACCEPT - Acalabrutinib Dipensing Log v1 10-Feb-17.pdf

ACCEPT - Drug Order Form v1 20-02-2017.pdf

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

SAE Documents

ACCEPT - Phase Ib Serious Adverse Event-SUSAR Report Form v2 10 Aug 2017

ACCEPT - SAE - SUSAR Follow-up Form v7 03-Feb-2016.pdf

ACCEPT - Section E Continuation - SAE SUSAR Report Form v4 05-Feb-2016.pdf

ACCEPT - Phase II SAE SUSAR Report Form v1 13-Apr-201

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