A surge of clinical trials with great potential for promising new treatments for T-cell lymphoma are based on significant basic research momentum made possible by a number of scientists and researchers, reports Dana-Farber Cancer Institute’s Insight blog.
A form of non-Hodgkin lymphoma (NHL), T-cell lymphoma occurs when immune system T cells begin growing and multiplying uncontrollably. With numerous types of the disease in all the entire group of them account for about 10% of NHL cases in America.
A group of new studies, some opened, some expected to open soon and some completed, represents a major thrust against the disease.
Back in 2015, Dana Farber’s David Weinstock, MD, led researchers at several institutions in receiving a prestigious SCOR (Specialized Center of Research) grant from the Leukemia and Lymphoma Society to support collaborative research into the disease. The grant was awarded to scientists at not only Dana-Farber but also other institutions and has underwritten research in laboratory cell lines and animal models and set the stage for the new wave of clinical research now underway.
Recent T-cell lymphoma Clinical Trials
- A phase 2 trial of the targeted drug ruxolitinib, which blocks signaling in the JAK/STAT pathway. Participants are divided into three groups: those with genetic evidence that the JAK/STAT pathway is active in their cancer cells; those with functional evidence that the pathway is active; and those without any evidence that it is active. The trial is helping investigators determine which patients are most likely to benefit from ruxolitinib, says Eric Jacobsen, MD, clinical director of the Lymphoma Programat Dana-Farber, who is leading the trial at the Institute.
- A trial of the oral drug duvelisib, which has already been approved for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma after other treatments have failed.
- A trial of ruxolitinib in combination with duvelisib to block both JAK/STAT and another pathway that may lead to resistance to ruxolitinib.
- A trial of the drug valemetostat, which targets the proteins EZH1 and EZH2, regulators of gene activity. This study builds on research from Weinstock’s laboratory that identified specific types of T-cell lymphoma that depend on EZH1 and EZH2.
- A trial of a compound called IPH4102, an antibody-based agent that targets the KIR3DL2 protein on the surface of T-cell lymphoma cells. Antibody agents have proved very effective in B-cell lymphomas but have not been carefully tested in patients with T-cell lymphoma.
Investigators are also in discussions to initiate a trial based on Weinstock’s discovery that adding a drug called AZD5991 to the standard four-drug regimen (known as CHOP) for T-cell lymphoma will increase the percent of patients who are cured of their lymphoma.
Traditionally, trials of potential drugs for T-cell lymphoma have been few and far between because the rarity of the disease, and the variety of forms it takes, has made it difficult to recruit sufficient numbers of participants. This series of new trials is beginning to change that. Jacobsen estimates they will collectively enroll more than 100 patients. Tissue samples from these patients are being tested by Weinstock to develop new drug combinations and innovative approaches that Jacobsen can then test in comprehensive program to improve the treatment of these diseases.