A(B)VD Followed by Nivolumab as Frontline Therapy for Higher Risk Patients With Classical Hodgkin Lymphoma (HL)

Inclusion Criteria:

- Cohort A overview: Patients age less than 60 with untreated stage III or IV classical
Hodgkin lymphoma will be eligible for cohort A. In phase I, patients could enroll onto
cohort A if they had have a baseline IPS ≥3 OR if their PET scan after 2 cycles of
ABVD is positive (Deauville 4 or 5). Enrollment onto phase I has now ceased and
enrollment will begin for phase II. In phase II, patients less than 60 years of age
with stage III or IV HL are eligible. Patients may enroll anytime within the first 2
cycles of ABVD or after PET-2.

- Cohort B overview: Patients 60 or older with untreated classical Hodgkin lymphoma
(regardless of stage) will be eligible for cohort B.

The following eligibility criteria applies to both cohort A and B except when stated
otherwise:

- Histologic diagnosis of classical Hodgkin lymphoma

- FDG-avid disease by FDG-PET/CT

- Ann Arbor Stage III or IV disease (Cohort A only)

- WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25
IU/L or equivalent units of HCG) within 2 weeks prior to the start of study drug.
Women who undergo fertility preservation within 2 weeks of beginning chemotherapy
are expected to have false-positive pregnancy tests and therefore testing may be
waived for these patients.

- WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25
IU/L or equivalent units of HCG) within 24 hours prior to the start of study
drug. Women who undergo fertility preservation within 2 weeks of beginning
chemotherapy are expected to have false-positive pregnancy tests and therefore
testing may be waived for these patients.

- Women must not be breastfeeding

- Men who are sexually active with WOCBP must agree to follow instructions for method(s)
of contraception for the duration of treatment with study drug plus 5 half-lives of
study drug plus 90 days (duration of sperm turnover) for a total of 31 weeks
posttreatment completion

- Age ≥ 18

- Serum creatinine ≤ 1.5 x Upper limit of normal (ULN) or creatinine clearance (CrCl) ≥
40 mL/min (measured using the Cockcroft-Gault formula

- AST/ALT ≤ 3 x ULN (5x ULN for those with lymphoma involvement of the liver)

- Total bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total
bilirubin < 3.0 mg/dL)

Exclusion Criteria:

- Subjects with active brain metastases or leptomeningeal metastases.

- Subjects with nodular lymphocyte-predominant HL

- Any serious or uncontrolled medical disorder that, in the opinion of the investigator,
may increase the risk associated with study participation or study drug
administration, impair the ability of the subject to receive protocol therapy, or
interfere with the interpretation of study results.

- Prior malignancy active within the previous 3 years except for locally curable cancers
that have been apparently cured, such as basal or squamous cell skin cancer,
superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.

- Subjects with active, known or suspected autoimmune disease. Subjects with 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 are permitted
to enroll.

- Subjects with a condition requiring systemic treatment with systemic corticosteroids
(equivalent of >10mg/day of prednisone). Patients may receive steroid therapy if
steroids are tapered down to 10mg or less by 4 weeks after initiating A(B)VD to
control lymphoma-related symptoms.

- Any of the following cardiovascular conditions or values within 6 months before the
first dose of study drug:

- A left-ventricular ejection fraction < 50%

- Myocardial infarction within 2 years of randomization

- New York Heart Association (NYHA) Class III or IV heart failure

- Evidence of current uncontrolled cardiovascular conditions, including cardiac
arrhythmias, congestive heart failure (CHF), angina, or electrocardiographic evidence
of acute ischemia or active conduction system abnormalities

- Any positive test for hepatitis B virus or hepatitis C virus indicating acute
infection.

- Known history of testing positive for human immunodeficiency virus (HIV) or known
acquired immunodeficiency syndrome (AIDS).

- History of severe hypersensitivity reaction to any monoclonal antibody.

- Adjusted DLCO <60%