First-in-human clinical trial evaluates safety of combination therapy to treat B-cell lymphomas

lymphoma cells

Lymphomas affect the immune system’s lymphocytes. A new clinical trial is set to explore a targeted combination therapy for multiple types of lymphoma.
Photo credit: NCI Visuals Online

A new phase I clinical trial to evaluate the safety and maximum tolerated dosage of a five-drug targeted combination therapy called ViPOR for patients with relapsed and treatment-resistant, or refractory, B-cell lymphomas is open at the National Institutes of Health (NIH) Clinical Center in Bethesda, Maryland. Individually, all five drugs have shown efficacy in battling lymphomas and certain blood cancers but are typically never used in combinations of more than two or three to treat these cancers.

“The current treatment for relapsed and refractory B-cell lymphomas is chemotherapy and antibody therapy together, which is known as chemoimmunotherapy, but this rarely provides long-term control of disease,” says Christopher Melani, M.D., Staff Clinician in the Lymphoid Malignancies Branch. “When a disease is resistant to chemoimmunotherapy, you need to try a different type of therapy.”

Lymphomas are cancers of lymphocytes, a type of white blood cell integral to the immune system.  There are more than 45 different types of lymphoma, including both Hodgkin and non-Hodgkin types. B-cell lymphomas are the most common non-Hodgkin type. Although many lymphomas respond well to traditional radiation and chemoimmunotherapy treatments with long-term remission rates as high as 90 percent, a large proportion of patients with certain aggressive lymphomas develop relapsed or refractory disease. Such patients rarely benefit from standard therapies.

This new trial, led by Dr. Melani, will determine the best dosage and potential side effects of a therapy called ViPOR, named for the combination of drugs it includes: venetoclax, ibrutinib, prednisone, obinutuzumab and revlimid.

Although each of the ViPOR drugs has shown some efficacy against lymphomas, they rarely cause these cancers to go into complete remission when administered alone. When used in combination, however, preclinical studies in human cancer cell lines and in mice with lymphoma have shown that the ViPOR drugs kills lymphoma cells more effectively than single-drug therapies and have the potential to act synergistically with each drug to magnify the cancer-fighting power of the others.

“By giving multiple agents at once, this prevents development of resistance to therapies,” says Dr. Melani. According to Melani, the approach has the potential to drive the lymphomas into deep and long-term remission, especially in patients who cannot tolerate, who don’t respond to or who relapse after standard chemoimmunotherapies.

ViPOR works by targeting and disrupting four key pathways used by cancerous lymphoma cells to grow and survive. “Unlike traditional chemotherapy treatments, which can disrupt DNA synthesis and cause many side effects, ViPOR targets specific proteins,” says Melani. “And for that reason, the drugs are likely to induce fewer side effects in patients.”

Giving patients a combination of five drugs does, however, raise the potential for synergistic side effects, but Melani and colleagues have designed their protocol to minimize such risk. “Giving this regimen in cycles, which include breaks in treatment, allows patients to recover from potential side effects before the next cycle of therapy,” Dr. Melani says. “Continuous administration as is done with monotherapy or doublet therapy does not generally give a break to allow recovery from side effects.”

Melani hopes to test ViPOR against as many different types of lymphoma as possible in the trial, so patient recruitment is key. Patients 18 and older with confirmed refractory or relapsed B-cell lymphoma who are interested in taking part in the study are encouraged to contact Maureen Edgerly, R.N., at 240-760-6013 to discuss their potential eligibility. Unfortunately, the study cannot accept patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and mantle cell lymphoma due to their risk of developing a life-threatening condition called tumor lysis syndrome.

“We’re very excited about this trial because the regimen has never been tried in humans before,” says Dr. Melani. “Our patients are extremely brave to be testing a new regimen with potential unknown side effects, but the hope of a benefit for treating their underlying disease when all other therapies have stopped working gives them the strength to participate in studies such as this. We hope in the end that it becomes a standard regimen that’s available to patients all over the world.”

For more about first-in-human trials at the NIH Clinical Center, watch the Discovery Channel’s documentary released this past summer.

The Center for Cancer Research is NCI’s internal cancer center, a publicly funded organization working to improve the lives of cancer patients by solving important, challenging and neglected problems in cancer research and patient care.  Highly trained physician-scientists develop and carry out clinical trials to create the medicines of tomorrow treating patients at the world’s largest dedicated research hospital on the campus of the National Institutes of Health in Bethesda, Maryland.  For more information on CCR clinical trials click here and subscribe to have the latest CCR clinical trials sent directly to your inbox.

Summary Posted: 02/2018