Title
Phase I/II Study of Nivolumab in Combination with Ruxolitinib in Relapsed or Refractory Classical Hodgkin Lymphoma

Description
Phase I Study of Nivolumab + Ruxolitinib in Relapsed/Refractory Classical Hodgkins Lymphoma

Objective
This study is being done to determine the maximum tolerated dose (highest dose) of ruxolitinib that can be given safely in combination with nivolumab. This study will also:

Measure the percentage of tumor (lymphoma) that shrank after receiving ruxolitinib in combination with nivolumab

Measure the length of time the lymphoma is inactive and

Study how safe the combination is to administer to participants.

Treatment If you are eligible and agree to participate, you will receive the study drugs as described below:

Nivolumab will be given once every four weeks. Nivolumab will be given through a vein (IV), which is also called an infusion

Ruxolitinib is a pill that you will take two times per day, every day

During the first cycle, you will take ruxolitinib for 1 week before you receive the first nivolumab infusion

The study drugs will be given in units of time called cycles. One cycle equals 28 days (4 weeks). The first 2 participants treated in the study will receive ruxolitinib at dose level 1 (10 mg twice a day). If participants do well at this dose for 35 days, then the next set of 2 will be enrolled at dose level 2 (15 mg twice daily). If they do well for 35 days then dose level 3(20 mg twice a day). If at any time the side effects experienced by patients are too severe, the dose level will be decreased

Key Eligibility
Aged 18 years or older

Histologically confirmed diagnosis of classical Hodgkin lymphoma that is relapsed or refractory, historical biopsy at last relapse is acceptable

Failed prior therapy with check-point inhibitors (nivolumab, pembrolizumab, others)

Failed at least two prior therapies –prior therapies include: cytotoxic chemotherapy including ABVD or similar, autologous transplantation,brentuximab vedotin, allogenic transplantation without active graft versus host disease

Radiographically measurable disease (defined as the presence of greater than or equal to 1.5 cm lesion, as measured in the longest dimension by PET/CT)

ECOG performance status 0 or 1

Adequate organ function as described by the protocol

Females of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of written consent until 5 months
after treatment discontinuation

Males who are sexually active with partners of child-bearing potential must be willing to abstain from heterosexual activity or adhere to contraception from the time of written consent until 7
months after treatment discontinuation

EXCLUSION:

Prior exposure to ruxolitinib

Pregnant or breastfeeding

Inability or unwillingness to swallow oral medication or any condition that precludes the administration and/or absorption of oral medications

Active central nervous system (CNS) involvement by lymphoma

Uncontrolled cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction

Concomitant therapy with immunosuppressive agents, including systemic corticosteroids (doses less than or equal to 10 mg/day prednisone or equivalent are permitted)

History of HIV infection

Active Hepatitis B or C infection

Currently active, clinically significant hepatic impairment Child-Pugh class B or C

History of stroke or intracranial hemorrhage within 6 months of study registration

Applicable Disease Sites
Lymphoma

Participating Institutions
UW Health 1 S. Park Medical Center; UW Health University Hospital