Dose Escalation Study to Determine the Maximum Tolerated Dose of the Combination of Ruxolitinib and Bortezomib in Patients With Relapsed or Refractory Lymphoma

Treatment of relapsed and refractory Hodgkin and Non-Hodgkin's Lymphoma remains difficult. To improve upon current efficacy rates new treatment modalities are needed. Currently modalities based upon targeting specific pathway and molecular receptors have made the greatest impact in the outcomes of refractory patients. The JAK-Stat pathway and NF-κB are two such targets that have been shown to fuel the malignant transformation and growth of both myeloma and lymphoma. Blockade of key points in these molecular pathways has the potential of halting the pro-survival machinery. Combined inhibition of JAK/Stat and NF-κB may lead to synergistic effects as well as possibly mitigating some of the mechanisms of resistance to either agent. In this proposal, the investigators aim to utilize the JAK/Stat inhibitor ruxolitinib (Jakafi) and proteasome inhibitor bortezomib (Velcade) to target two major pathways of malignant transformation in hematologic malignancies. The primary objective of this research study is to determine the maximum tolerated dose (MTD) of Ruxolitinib (Jakafi) in combination with standard dose Bortezomib (Velcade) in patients with relapsed or refractory Hodgkin (HL) and Non-Hodgkin Lymphoma (NHL). The University of Michigan will enroll 24 subjects. Eligible subjects will have histologically or cytologically confirmed Hodgkin and Non-hodgkin's Lymphoma excluding Burkitt, CLL and lymphoblastic lymphoma that is considered to have relapsed or to be refractory to primary chemotherapy. Any prior exposure to Jakafi is excluded.