March 8, 2019:

A phase I Big Ten Cancer Research Consortium study for adult patients with relapsed or refractory Classical Hodgkin lymphoma is open for accrual at Masonic Cancer Center, University of Minnesota; the University of Illinois Cancer Center; the University of Wisconsin Carbone Cancer Center; and the University of Iowa Holden Comprehensive Cancer Center. The study, BTCRC-HEM15-027, will help determine the safety (maximum tolerated dose) and efficacy of ruxolitinib, which blocks the main pathway dysregulated in Hodgkin lymphoma, when combined with the immunotherapy drug nivolumab.

Hodgkin lymphoma is a blood cancer involving the lymphoreticular system which presents with swollen lymph nodes, mediastinal mass, or organ infiltration by cancer cells.

Patients with Hodgkin lymphoma are often treated with chemotherapy drugs, radiation therapy, stem cell transplantation, or a combination of these treatments. Currently, brentuximab vedotin or nivolumab are approved treatments for Hodgkin lymphoma, and researchers are exploring alternatives that could work more effectively.

“Recent molecular insight in how Hodgkin lymphoma develops has led to the recognition that two unique genes are abnormally regulated with Hodgkin lymphoma,” said Veronika Bachanova, MD, PhD (pictured), sponsor-investigator of this study and a hematologist-oncologist at Masonic Cancer Center, University of Minnesota.

Dr. Bachanova said that scientists don’t know what triggers the genetic changes, but they now understand that almost all Hodgkin lymphoma cancers possess specific abnormalities in chromosome 9.

This affects two pathways — PD-1, a checkpoint pathway, and the gene Janus Kinase 2 (JAK2), which provides instructions for making a protein that promotes the growth and proliferation of cells. Both of these pathways are altered in Hodgkin lymphoma cancer cells.

“Amplification of the JAK2 gene and PD-L1 in chromosome 9 results in making too many copies of these genes, and subsequent high levels of proteins provide signals to support uncontrolled growth of Hodgkin lymphoma cancer cells.” she said.

The immunotherapy drug nivolumab will be used in this study to block the PD-1 pathway, which cancer cells often use to escape from the body’s immune system. By blocking the PD-1 pathway, nivolumab helps the immune system to recognize and kill cancer cells. Ruxolitinib will be used to target JAK2 genes, which send signals that promote the growth of cancers.

Dr. Bachanova believes the synergism of the chosen drugs is critical and the combination may work better together than independently.

“Based upon knowledge of the biology and genetics which has recently been identified, we think blocking the pathway will make the Hodgkin lymphoma cancer cells more susceptible to checkpoint inhibitors,” she said. “Combination trials can enhance the efficacy of checkpoint inhibitors or even overcome resistance to PD-1 inhibitors.”

Nivolumab is approved by the U.S. Food and Drug Administration (FDA) for use in several cancer types, including classical Hodgkin lymphoma. Ruxolitinib is approved by the FDA for the treatment of two bone marrow diseases, myelofibrosis and polycythemia vera. The combination of ruxolitinib and nivolumab has not been approved by the FDA for use in classical Hodgkin lymphoma and should be considered investigational.

This study is supported by Incyte and Bristol-Myers Squibb.

Up to 20 subjects will be enrolled in this study in cohorts of 2 patients. All participants will receive the same dose of nivolumab. Each new cohort will receive the currently enrolling dose level of ruxolitinib. The study doctor will inform participants of their assigned dose level when they begin the study. Neither the subject nor the doctor can choose the dose, but doses may be adjusted if a participant experiences problems or side effects.

Tissue samples will also be collected for correlative research. Investigators will look for changes or mutations in subjects’ genes and compare the results with how well the drugs worked on their tumor. They will also archive some tissue for ongoing research.

Participants must be 18 or older and have either relapsed or refractory Hodgkin lymphoma. For more information about this study, including full eligibility requirements, visit: www.clinicaltrials.gov (study #NCT03681561).

About the Big Ten Cancer Research Consortium: The Big Ten Cancer Research Consortium was created in 2013 to transform the conduct of cancer research through collaborative, hypothesis-driven, highly translational oncology trials that leverage the scientific and clinical expertise of Big Ten universities. The goal of the Big Ten Cancer Research Consortium is to create a unique team-research culture to drive science rapidly from ideas to new approaches to cancer treatment. Within this innovative environment, today’s research leaders collaborate with and mentor the research leaders of tomorrow with the unified goal of improving the lives of all patients with cancer.

About the Big Ten Conference: The Big Ten Conference is an association of world-class universities whose member institutions share a common mission of research, graduate, professional and undergraduate teaching and public service. Founded in 1896, the Big Ten has sustained a comprehensive set of shared practices and policies that enforce the priority of academics in the lives of students competing in intercollegiate athletics and emphasize the values of integrity, fairness and competitiveness. The broad-based programs of the 14 Big Ten institutions will provide over $200 million in direct financial support to almost 9,500 students for more than 11,000 participation opportunities on 350 teams in 42 different sports. The Big Ten sponsors 28 official conference sports, 14 for men and 14 for women, including the addition of men’s ice hockey and men’s and women’s lacrosse since 2013. For more information, visit www.bigten.org.