{"id":11622,"date":"2019-03-08T15:11:15","date_gmt":"2019-03-08T21:11:15","guid":{"rendered":"https:\/\/cancer.wisc.edu\/research\/?p=11622"},"modified":"2019-07-08T15:12:19","modified_gmt":"2019-07-08T20:12:19","slug":"big-ten-crc-study-to-help-determine-maximum-dosage-of-ruxolitinib-when-combined-with-nivolumab-in-hodgkin-lymphoma-patients","status":"publish","type":"post","link":"https:\/\/wwwtest.cancer.wisc.edu\/research\/big-ten-crc-study-to-help-determine-maximum-dosage-of-ruxolitinib-when-combined-with-nivolumab-in-hodgkin-lymphoma-patients\/","title":{"rendered":"Big Ten CRC study to help determine maximum dosage of ruxolitinib when combined with nivolumab in Hodgkin lymphoma patients"},"content":{"rendered":"

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,\u00a0BTCRC-HEM15-027<\/a>, 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.<\/span><\/p>\n

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

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.<\/p>\n

\u201cRecent molecular insight in how Hodgkin lymphoma develops has led to the recognition that two unique genes are abnormally regulated with Hodgkin lymphoma,\u201d said Veronika Bachanova, MD, PhD (pictured), sponsor-investigator of this study and a hematologist-oncologist at\u00a0Masonic Cancer Center, University of Minnesota<\/a>.<\/p>\n

Dr. Bachanova said that scientists don\u2019t know what triggers the genetic changes, but they now understand that almost all Hodgkin lymphoma cancers possess specific abnormalities in chromosome 9.<\/p>\n

This affects two pathways \u2014 PD-1, a checkpoint pathway, and the gene\u00a0Janus Kinase 2 (JAK2)<\/em>, 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.<\/p>\n

\u201cAmplification of the\u00a0JAK2<\/em>\u00a0gene 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.\u201d she said.<\/p>\n

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\u2019s 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\u00a0JAK2<\/em>\u00a0genes, which send signals that promote the growth of cancers.<\/p>\n

Dr. Bachanova believes the synergism of the chosen drugs is critical and the combination may work better together than independently.<\/p>\n

\u201cBased 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,\u201d she said. \u201cCombination trials can enhance the efficacy of checkpoint inhibitors or even overcome resistance to PD-1 inhibitors.\u201d<\/p>\n

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.<\/p>\n

This study is supported by Incyte and Bristol-Myers Squibb.<\/p>\n

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.<\/p>\n

Tissue samples will also be collected for correlative research. Investigators will look for changes or mutations in subjects\u2019 genes and compare the results with how well the drugs worked on their tumor. They will also archive some tissue for ongoing research.<\/p>\n

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:\u00a0www.clinicaltrials.gov<\/a>\u00a0(study #NCT03681561<\/a>).<\/p>\n","protected":false},"excerpt":{"rendered":"

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 …<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_mi_skip_tracking":false,"_exactmetrics_sitenote_active":false,"_exactmetrics_sitenote_note":"","_exactmetrics_sitenote_category":0},"categories":[125],"tags":[],"acf":[],"_links":{"self":[{"href":"https:\/\/wwwtest.cancer.wisc.edu\/research\/wp-json\/wp\/v2\/posts\/11622"}],"collection":[{"href":"https:\/\/wwwtest.cancer.wisc.edu\/research\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/wwwtest.cancer.wisc.edu\/research\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/wwwtest.cancer.wisc.edu\/research\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/wwwtest.cancer.wisc.edu\/research\/wp-json\/wp\/v2\/comments?post=11622"}],"version-history":[{"count":1,"href":"https:\/\/wwwtest.cancer.wisc.edu\/research\/wp-json\/wp\/v2\/posts\/11622\/revisions"}],"predecessor-version":[{"id":11623,"href":"https:\/\/wwwtest.cancer.wisc.edu\/research\/wp-json\/wp\/v2\/posts\/11622\/revisions\/11623"}],"wp:attachment":[{"href":"https:\/\/wwwtest.cancer.wisc.edu\/research\/wp-json\/wp\/v2\/media?parent=11622"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/wwwtest.cancer.wisc.edu\/research\/wp-json\/wp\/v2\/categories?post=11622"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/wwwtest.cancer.wisc.edu\/research\/wp-json\/wp\/v2\/tags?post=11622"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}