The University of Southampton in Britain is leading a Phase 1/2 clinical trial to test whether adding acalabrutinib to R-CHOP can improve outcomes for patients with diffuse large B-cell lymphoma (DLBCL).
R-CHOP, the standard therapy for DLBCL, consists of a combination of rituximab, an anti-CD20 monoclonal antibody that targets B-cells, and four chemotherapy drugs. This immunochemotherapy can be effective for some patients, but in others the cancer either does not fully respond or comes back after a period of remission.
Acalabrutinib is a tyrosine kinase inhibitor (TKI) being developed by Acerta Pharma, the hematology branch of AstraZeneca. It acts by blocking a protein that plays a significant role in preventing cells from dying, to help kill or slow the progression of lymphoma cells. Its mode of action is similar to that of ibrutinib, another TKI used in lymphoma.
“Results from previous trials that use acalabrutinib to fight other blood cancers have been very promising,” Andrew Davies, the trial’s lead researcher and an associate professor in medical oncology at the University of Southampton, said in a press release. “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.”
The ACCEPT trial, taking place in Britain and supported by Cancer Research UK, is underway at centers in Leeds, London, Nottingham, Oxford, Plymouth, and Southampton. Researchers are looking to recruit about 40 people, ages 16 and older, with stage 1–4 and previously untreated DLBCL that is CD20-positive. All need to be healthy enough to undergo a full course of R-CHOP, which will be given to all trial participants as a standard DLBCL treatment.
In Phase 1, researchers will divide patients into two groups to assess the safety of acalabrutinib and determine which of two doses is most tolerable. Patients will be monitored through blood and other tests, and body scans. The best dose, if identified, will then be tested in another group of about 15 patients in the trial’s Phase 2 portion, which will further investigate safety, side effects, and how well acalabrutinib works.
The trial is recruiting patients at the six sites through January 2020. Information is available on the trial’s Cancer Research UK webpage.
Trial researchers will also gather data on gene expression in these DLBCL patients as part of the Precision Medicine for Aggressive Lymphoma Consortium (PMAL), which aims to improve lymphoma diagnosis and treatment. Information collected will be added to a database for precision medicine, aiming to eventually match patients to targeted therapies using genetic profiles.
The U.S. Food and Drug Administration recently granted acalabrutinib priority review and breakthrough therapy designation for mantle cell lymphoma, a rarer type of B-cell lymphoma.
