PET-Directed Therapy With Pembrolizumab and Combination Chemotherapy in Treating Patients With Previously Untreated Classical Hodgkin Lymphoma

Inclusion Criteria:

   - Patients must have a histologically confirmed diagnosis of classical Hodgkin lymphoma
   including nodular sclerosis, mixed cellularity, lymphocytic-rich, and lymphocyte
   depleted subtypes by the 4th edition of the World Health Organization (WHO)
   Classification of Tumors of Hematopoietic and Lymphoid Tissues published in 2008
   (nodular lymphocyte-predominant Hodgkin lymphoma [NLPHL] excluded)

   - Patients must have measurable disease by the Lugano criteria

   - Patients must have previously untreated disease (except for one week or less of
   corticosteroids)

   - Patients must exhibit a/an Eastern Cooperative Oncology Group (ECOG) performance
   status of 0-1

   - Patients may have any stage and any International Prognostic Score (IPS)

   - Patients must have adequate organ and bone marrow function within 14 days prior to
   registration, as defined below:

   - Leukocytes >= 3,000/mcL

   - Absolute neutrophil count >= 1,500/mcL

   - Platelets >= 100,000/mcl

   - Total bilirubin within normal institutional limits

   - Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase
   [SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT])
   =< 2.5 X institutional upper limit of normal (ULN)

   - Creatinine within normal institutional limits

   - Platelet transfusions are acceptable prior to treatment to achieve the above numbers,
   however growth factors are not allowed within 14 days of registration

   - Females of child-bearing potential (FOCBP) and males must agree to avoid becoming
   pregnant, or impregnating a partner, respectively, by complying with any of the
   approved contraception techniques prior to registration, for the duration of study
   participation, and for 120 days following completion of therapy; abstinence is
   acceptable if this is the usual lifestyle and preferred contraception for the subject;
   should a female patient become pregnant or suspect she is pregnant while participating
   in this study, she should inform her treating physician immediately

NOTE: A FOCBP is any woman (regardless of sexual orientation, having undergone a tubal
ligation, or remaining celibate by choice) who meets the following criteria:

   - Has not undergone a hysterectomy or bilateral oophorectomy

   - Has had menses at any time in the preceding 12 consecutive months (and therefore has
   not been naturally postmenopausal for > 12 months)

      - FOCBP must have a negative pregnancy test within 7 days prior to registration on
      study; NOTE: a negative pregnancy test is also required within 3 days prior to
      first dose of pembrolizumab and therefore may need to be repeated if screening
      test is more than 3 days prior to first dose

      - Patients must have the ability to understand and the willingness to sign a
      written informed consent prior to registration on study

Exclusion Criteria:

   - Patients are not eligible who have had prior chemotherapy, targeted small molecule
   therapy, or radiation therapy within 2 weeks prior to registration or who have not
   recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously
   administered agent

      - NOTE: Subjects with =< grade 2 neuropathy are an exception to this criterion and
      may qualify for the study

      - NOTE: If subject received major surgery, they must have recovered adequately from
      the toxicity and/or complications from the intervention prior to starting therapy

   - Patients who have a diagnosis of immunodeficiency or are receiving systemic steroid
   therapy or any other form of immunosuppressive therapy within 7 days prior to
   registration are not eligible

   - Patients who have a known history of active TB (bacillus tuberculosis) are not
   eligible

   - Patients must not have a history of allergic reactions attributed to compounds of
   similar chemical or biologic composition to pembrolizumab

   - Patients who have an uncontrolled intercurrent illness including, but not limited to
   any of the following, are not eligible:

      - Symptomatic congestive heart failure

      - Unstable angina pectoris

      - Cardiac arrhythmia

   - Patients who have a known additional malignancy that is progressing or requires active
   treatment are not eligible

      - NOTE: Exceptions include basal cell carcinoma of the skin or squamous cell
      carcinoma of the skin that has undergone potentially curative therapy or in situ
      cervical cancer

   - Patients who have known active central nervous system (CNS) metastases and/or
   carcinomatous meningitis are not eligible

      - NOTE: Subjects with previously treated brain metastases may participate provided
      they are stable (without evidence of progression by imaging for at least four
      weeks prior to the first dose of trial treatment and any neurologic symptoms have
      returned to baseline), have no evidence of new or enlarging brain metastases, and
      are not using steroids for at least 7 days prior to registration; this exception
      does not include carcinomatous meningitis which is excluded regardless of
      clinical stability

   - Patients who have active autoimmune disease that has required systemic treatment in
   the past 2 years are not eligible (i.e. with use of disease modifying agents,
   corticosteroids or immunosuppressive drugs)

      - NOTE: Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid
      replacement therapy for adrenal or pituitary insufficiency, etc.) is not
      considered a form of systemic treatment

   - Patients who have known history of, or any evidence of active, non-infectious
   pneumonitis are not eligible

   - Patients who have an active infection requiring systemic therapy are not eligible,
   except for uncomplicated urinary tract infections

   - Patients are not eligible who have a history or current evidence of any condition,
   therapy, or laboratory abnormality that might confound the results of the trial,
   interfere with the subject?s participation for the full duration of the trial, or is
   not in the best interest of the subject to participate, in the opinion of the treating
   investigator

   - Patients who have known psychiatric or substance abuse disorders that would interfere
   with cooperation with the requirements of the trial are not eligible

   - Patients may not be pregnant or breastfeeding, or expecting to conceive or father
   children within the projected duration of the trial, from registration through 120
   days after the last dose of trial treatment

   - Patients who have received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2
   agent are not eligible

   - Patients who have a known history of human immunodeficiency virus (HIV) (HIV 1/2
   antibodies) are not eligible

   - Patients who have active hepatitis B (e.g., hepatitis B virus surface antigen [HBsAg]
   reactive) or hepatitis C (e.g., hepatitis c virus [HCV] ribonucleic acid [RNA]
   [qualitative] is detected) are not eligible

   - Patients who received a live vaccine within 30 days of planned start of study therapy
   are not eligible; examples of live vaccines include, but are not limited to, the
   following: measles, mumps, rubella, varicella/zoster, yellow fever, rabies, bacillus
   Calmette-Guerin (BCG), and typhoid vaccine

      - NOTE: Seasonal influenza vaccines for injection are generally inactivated flu
      vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist)
      are live attenuated vaccines, and are not allowed