Nivolumab and Brentuximab Vedotin in Treating Older Patients With Untreated Hodgkin Lymphoma

Inclusion Criteria:

   - Classical Hodgkin lymphoma determined by local hematopathology review

   - One of the following:

      - Age >= 60 years

      - Age < 60 years but unsuitable for standard chemotherapy because of a cardiac
      ejection fraction of < 50%, a pulmonary diffusion capacity < 80%, or a creatinine
      clearance >= 30 and < 60 mL/min, or refused standard chemotherapy despite efforts
      to convince them otherwise

   - Requirement for systemic chemotherapy: all stages except IA (not bulky disease), if
   involved field is considered radiotherapy (RT) curative

   - Previously untreated with either chemotherapy, radiation therapy or either brentuximab
   vedotin or nivolumab, or another check point inhibitor

   - Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2

   - Absolute neutrophil count (ANC) >= 1500/mm^3, unless secondary to bone marrow
   involvement; obtained =< 7 days prior to registration

   - Leukocytes >= 3,000/mm^3, obtained =< 7 days prior to registration

   - Platelet count >= 100,000/mm^3, obtained =< 7 days prior to registration

   - Hemoglobin > 9.0 g/dL - unless determined by treating physician to be disease related,
   obtained =< 7 days prior to registration

   - Total bilirubin =< 1.5 x upper limit of normal (ULN), obtained =< 7 days prior to
   registration

   - Aspartate aminotransferase (aspartate transaminase [AST]) =< 2.5 x ULN, obtained =< 7
   days prior to registration

   - Alanine aminotransferase (alanine transaminase [ALT]) =< 2.5 x ULN, obtained =< 7 days
   prior to registration

   - Creatinine =< 2.0 mg/dL, obtained =< 7 days prior to registration

   - Amylase and/or lipase =< 1.5 x ULN, obtained =< 7 days prior to registration

   - Women of childbearing potential must have a negative serum or urine pregnancy test
   (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin
   [HCG]) within 24 hours prior to registration

      - Note: women of child-bearing potential (WOCBP) must use appropriate method(s) of
      contraception; WOCBP should use an adequate method to avoid pregnancy for 23
      weeks (30 days plus the time required for nivolumab to undergo five half-lives)
      after the last dose of investigational drug; men who are sexually active with
      WOCBP must use any contraceptive method with a failure rate of less than 1% per
      year; men receiving nivolumab and who are sexually active with WOCBP will be
      instructed to adhere to contraception for a period of 31 weeks after the last
      dose of investigational product; women who are not of childbearing potential
      (i.e., who are postmenopausal or surgically sterile) as well as azoospermic men
      do not require contraception; should a woman become pregnant or suspect she is
      pregnant while participating in this study, she should inform her treating
      physician immediately

   - Willing to return to enrolling institution for follow-up (during the active monitoring
   phase of the study)

      - Note: during the active monitoring phase of a study (i.e., active treatment and
      observation), participants must be willing to return to the consenting
      institution for follow-up

   - Ability to understand and willingness to sign an informed written consent

   - Provide blood and tissue samples for mandatory correlative research purposes

Exclusion Criteria:

   - Any of the following because this study involves an investigational agent whose
   genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are
   unknown:

      - Pregnant women

      - Nursing women

      - Men or women of childbearing potential who are unwilling to employ adequate
      contraception

   - Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
   of the investigator, would make the patient inappropriate for entry into this study or
   interfere significantly with the proper assessment of safety and toxicity of the
   prescribed regimens

   - Active, known or suspected autoimmune disease; note: subjects are permitted to enroll
   if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to
   autoimmune condition only requiring hormone replacement, psoriasis not requiring
   systemic treatment, or conditions not expected to recur in the absence of an external
   trigger

   - Use of systemic treatment with either corticosteroids (> 10 mg daily prednisone
   equivalents) or other immunosuppressive medications =< 14 days of registration; Note:
   Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone
   equivalents are permitted in the absence of active autoimmune disease

   - Immunocompromised patients, patients with known history of testing positive for human
   immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) and
   currently receiving antiretroviral therapy, patients with a prior history of known or
   suspected autoimmune disease, active hepatitis B virus surface antigen (HBV sAg+),
   active hepatitis C (if antibody [Ab]+ then polymerase chain reaction [PCR]+)
   indicating acute or chronic infection, and/or history of interstitial lung disease

   - Allergy to brentuximab vedotin and/or nivolumab

   - Uncontrolled intercurrent illness including, but not limited to, ongoing or active
   infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
   arrhythmia, or psychiatric illness/social situations that would limit compliance with
   study requirements

   - Receiving any other investigational agent which would be considered as a treatment for
   the primary neoplasm

   - Have had prior chemotherapy or radiotherapy for Hodgkin lymphoma

   - Have received either of the study drugs

   - < 60 years who are considered candidates for standard chemotherapy

   - >= grade 2 peripheral neuropathy

   - Other active malignancy =< 2 years prior to registration, unless treated with curative
   intent; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix;
   NOTE: if there is a history or prior malignancy, they must not be receiving other
   specific treatment for their cancer

   - Active central nervous system (CNS) involvement or leptomeningeal metastases
   involvement

   - Known history of pancreatitis