Nivolumab With Ruxolitinib in Relapsed or Refractory Classical Hodgkin Lymphoma

Inclusion Criteria:

• Written informed consent and HIPAA authorization for release of personal healthinformation. NOTE: HIPAA authorization may be included in the informed consent orobtained separately.

• Age ≥ 18 years at the time of consent.

• ECOG Performance Status of 0, 1 or 2.

• Histologically confirmed diagnosis of classical Hodgkin lymphoma that is relapsed orrefractory - historical biopsy at last relapse is acceptable. NOTE: a repeat biopsyis not required for Phase I if the historical biopsy was performed at the mostrecent relapse, without remission in between. A fresh biopsy is not required forPhase II.

• Presence of radiographically measurable disease (defined as the presence one or more ≥ 1.5 cm lesions, as measured in the longest dimension by PET/CT) within 4 weeks ofstudy registration.

• Prior therapy with check-point inhibitors (nivolumab, pembrolizumab, others) andsubsequent progressive disease, stable disease, mixed response, or relapse

• Failed at least one prior therapy

• Prior cancer treatment must be completed at least 14 days prior to registration andthe patient must have recovered from all reversible acute toxic effects of theregimen (other than alopecia) to ≤Grade 1 or baseline. Radiation therapy must becompleted at least 7 days prior to registration.

• Absolute Neutrophil Count ≥ 1000/μL

• Platelets ≥ 75,000/μL (or ≥50,000/mm3 if known BM involvement)

• Calculated creatinine clearance ≥ 40 cc/min using the Cockcroft-Gault formula

• Bilirubin ≤ 1.5 x upper limit of normal (ULN)

• Aspartate aminotransferase (AST) ≤ 2.5 × ULN

• Alanine aminotransferase (ALT) ≤ 2.5 × ULN

• Females of childbearing potential must have a negative serum pregnancy test within 7days prior to registration. NOTE: Females are considered of child bearing potentialunless they are surgically sterile (have undergone a hysterectomy, bilateral tuballigation, or bilateral oophorectomy) or they are naturally postmenopausal for atleast 12 consecutive months

• Males who are sexually active with partners of child-bearing potential must bewilling to abstain from heterosexual activity or adhere to contraception from thetime of written consent until 7 months after treatment discontinuation.

• Patient must provide voluntary written informed consent prior to the performance ofany research related tests or procedures.

Exclusion Criteria:

• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use whilethe mother is being treated on study).

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

• A life-threatening illness, medical condition or organ system dysfunction, which inthe investigator's opinion, could compromise the patient's safety, interfere withthe metabolism of study drugs, or put the study outcomes at undue risk

• Active central nervous system (CNS) involvement by lymphoma

• Uncontrolled cardiovascular disease such as uncontrolled or symptomatic arrhythmias,congestive heart failure, or myocardial infarction or any class 3 or 4 cardiacdisease as defined by the New York Heart Association Functional Classification

• Concomitant therapy with immunosuppressive agents, including systemiccorticosteroids (doses ≤ 10 mg/day prednisone or equivalent are permitted).

• Has a history of autoimmune disease now or in past 3 years such as hepatitis,nephritis, hyperthyroidism, interstitial lung disease or colitis except vitiligo oralopecia, hypothyroidism (eg, following Hashimoto syndrome) stable on hormonereplacement or psoriasis not requiring systemic treatment

• HIV-infected patients on effective anti-retroviral therapy with undetectable viralload within 6 months of registration are eligible for this trial.

• Active Hepatitis B or C infection (defined as a positive Hepatitis B surface antigen (Ag) or detectable viral load by PCR). NOTES: Hepatitis B and C testing is required.Patients with positive Hepatitis B Ag may enroll if PCR is negative. Suppressiveantiviral therapy should be considered for these patients as clinically indicated.

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

• Currently receiving a strong CYP3A4 Inhibitor (such as but not limited to boceprevirclarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole,lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir,saquinavir, telaprevir, telithromycin, voriconazole) or Fluconazole >200 mg/day.Washout period of 1 week is required.

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