Nivolumab and Ruxolitinib in Treating Patients with Relapsed or Refractory Classic Hodgkin Lymphoma

Inclusion Criteria

• Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately
• Age >= 18 years at the time of consent
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Histologically confirmed diagnosis of classical Hodgkin lymphoma that is relapsed or refractory - historical biopsy at last relapse is acceptable. NOTE: a repeat biopsy is not required for Phase I if the historical biopsy was performed at the most recent relapse, without remission in between. A fresh biopsy is not required for phase II
• Presence of radiographically measurable disease (defined as the presence one or more >= 1.5 cm lesions, as measured in the longest dimension by positron emission tomography [PET]/computed tomography [CT]) within 4 weeks of study registration
• Prior therapy with check-point inhibitors (nivolumab, pembrolizumab, others) and subsequent progressive disease, stable disease or mixed response
• Failed at least 2 prior therapies - prior therapies include: * Cytotoxic chemotherapy including doxorubicin hydrochloride, bleomycin, vinblastine and dacarbazine (ABVD) or similar * Autologous transplantation * Brentuximab vedotin * Allogenic transplantation without active graft versus host disease * Note: Patients who are eligible and willing to undergo autologous transplant should not be enrolled on this trial
• Prior cancer treatment must be completed at least 14 days prior to registration and the patient must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to =< grade 1 or baseline. Radiation therapy must be completed at least 7 days prior to registration
• Absolute neutrophil count (ANC) >= 1000/uL (obtained within 14 days prior to registration)
• Platelets (PLT) >= 75,000/uL (or >= 50,000/mm^3 if known bone marrow [BM] involvement) (obtained within 14 days prior to registration)
• Calculated creatinine clearance >= 40 cc/min using the Cockcroft-Gault formula (obtained within 14 days prior to registration)
• Bilirubin =< 1.5 x upper limit of normal (ULN) (obtained within 14 days prior to registration)
• Aspartate aminotransferase (AST) =< 2.5 x ULN (obtained within 14 days prior to registration)
• Alanine aminotransferase (ALT) =< 2.5 x ULN (obtained within 14 days prior to registration)
• Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to registration. NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months
• Females of childbearing potential and males with partners of child-bearing 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 at least 5 months after nivolumab discontinuation. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method
• 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
• Patient must provide voluntary written informed consent prior to the performance of any research related tests or procedures

Exclusion Criteria

• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study)
• Inability or unwillingness to swallow oral medication or any condition that precludes the administration and/or absorption of oral medications
• A life-threatening illness, medical condition or organ system dysfunction, which in the investigator’s opinion, could compromise the patient’s safety, interfere with the 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 cardiac disease as defined by the New York Heart Association Functional Classification
• Concomitant therapy with immunosuppressive agents, including systemic corticosteroids (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 or alopecia, hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement or psoriasis not requiring systemic treatment
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load 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 polymerase chain reaction [PCR]). NOTES: Hepatitis B and C testing is required. Patients with positive hepatitis B Ag may enroll if PCR is negative. Suppressive antiviral 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 boceprevir clarithromycin, 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