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Experimental drug trial seeks to improve treatment for lymphoma

Published: 
11 August 2017
lymphoma cells
Experimental drug trial seeks to improve treatment for lymphoma

Patients with a common type of fast-growing cancer are being given fresh hope in a new clinical trial.

Scientists at the University of Southampton are, for the first time, to trial a new experimental drug, in combination with immunochemotherapy, in certain patients with diffuse large B-cell lymphoma (DLBCL).

DLBCL is the most common type of fast-growing non-Hodgkin lymphoma. For many people, the standard treatment, called R-CHOP, uses a combination of an immunotherapy called rituximab and four chemotherapy drugs to find and destroy lymphoma cells. But sometimes DLBCL does not go away, or comes back after a period of remission.

Researchers at the University of Southampton want to find out whether a new protein inhibitor called acalabrutinib* improves patient response to standard treatments. Acalabrutinib is being developed by Acerta Pharma, a member of the AstraZeneca group.

The ACCEPT trial, which has launched at seven centres** across the country and is being funded by Acerta Pharma, will be managed by the Southampton Clinical Trials Unit, and will for the first time combine acalabrutinib with R-CHOP***.

The first phase of the trial will help determine a safe and tolerable dose of the drug. Patients will receive multiple low doses of acalabrutinib, while samples of blood and other fluids, collected at various time points, are analysed for information on how the body processes the drug in combination with R-CHOP.  

The subsequent phase will evaluate whether this treatment combination is effective at treating DLBCL and preventing its return.

Researchers on this trial are accepting patients aged 16 years and above, with previously untreated CD20 positive**** diffuse large B-cell lymphoma, requiring a full course of chemotherapy.

Dr Andrew Davies, lead researcher on the trial and associate professor and consultant in medical oncology at the University of Southampton, said: “For some lymphoma patients standard treatments are not effective, so we urgently need trials like this to help more people survive their disease.

“Results from previous trials that use acalabrutinib to fight other blood cancers have been very promising. This new and unique drug combination will attack the cancer from two sides. Not only will it mark the cancer cells so the immune system can find them and kill them, but it will also prevent the activity of key proteins that play an important role in the spread and survival of malignant B cells. We believe this new combination will benefit patients in addition to standard treatment.”

ACCEPT is the first clinical trial to be run as part of the Precision Medicine for Aggressive Lymphoma Consortium (PMAL).***** Gene expression data gathered as part of this trial will be used by PMAL to improve diagnosis and treatment for lymphoma. It will contribute to a sophisticated database which could one day match patients to targeted therapies based on genetic profiling. 

Professor Peter Johnson, director of the Southampton Cancer Research UK Centre, said: “Our research into the molecular changes that make lymphomas grow has given us important new leads on how we might treat them more effectively. 

“This trial is exciting because it uses a new targeted cancer drug to switch off key signals in lymphoma cells, and at the same time we will be able to collect information about whether this is a good approach for more patients in the future.”

Related Staff Member

Notes for editors

*On 01 August 2017, acalabrutinib was recently given Breakthrough Therapy Designation (BTD) by the US Food and Drug Administration for the treatment of a non-Hodgkin lymphoma called Mantle cell Lymphoma.  It works by blocking the action of a B-cell associated protein called Bruton tryrosine kinase (BTK). Clinical studies have shown that inhibiting BTK with a drug called ibrutinib (a currently approved BTK inhibitor) in combination with R-CHOP chemotherapy for previously untreated B-cell non Hodgkin lymphoma is safe. Acalabrutinib is BTK inhibitor in development that has shown increased target selectivity compared to ibrutinib. 

**The ACCEPT trial will take place at the Universities of Southampton, Plymouth, Oxford, Nottingham, UCL, Leeds Teaching Hospitals NHS Trust - St James's University Hospital and the Manchester Christie Hospital. 

***R-CHOP is a combination of an immunotherapy called rituximab and four chemotherapy drugs called Cyclophosphamide, doxorubicin, vincristine and prednisolone.

****Rituximab targets a protein called CD20 on the surface of lymphoma cells. The antibody sticks to all the CD20 proteins it finds. Then the cells of the immune system pick out the marked cells and kill them.

***** http://www.southampton.ac.uk/ctu/trialportfolio/listoftrials/pm-al.page

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