Pembrolizumab and Involved Site Radiation Therapy for Early Stage Relapsed or Primary Refractory Hodgkin Lymphoma

Inclusion Criteria:

- Three populations of patients are eligible for enrollment:

(1) Patients with early stage disease at diagnosis (stage I-II) who were treated with
chemotherapy alone and relapsed with early stage disease (stage RI-II).

(2) Patients with early stage disease at diagnosis (stage I-II) who were treated with
chemotherapy alone and have early stage (stage RI-II) primary refractory disease
(residual disease on a scan 1 month after the completion of initial therapy) without
B-symptoms and with each area of disease less than 10 cm in size.

(3) Patients with early stage disease at diagnosis (stage I-II) who were treated with
combined modality therapy (chemotherapy and radiation) who relapse with early stage
disease (stage RI-II) outside the prior radiation therapy field.

- Histologic confirmation of classical Hodgkin Lymphoma after imaging documenting
primary refractory or relapsed disease

- Age 18 or older

- ECOG Performance Status of 0-1

- Adequate organ function. Screening labs should be performed within 14 days of
treatment initiation.

Hematologic

- Absolute neutrophil count (ANC) ≥1,000 /mcL

- Platelets* ≥75,000 / mcL

- Hemoglobin* ≥8 g/dL Renal

- Creatinine OR Measured or calculated** creatinine clearance CrCl (GFR can also be used
in place of creatinine or ≤1.5 X upper limit of normal (ULN) OR ≥60 mL/min for subject
with creatinine levels > 1.5 X institutional ULN Hepatic

- Total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total
bilirubin levels >1.5 ULN

- AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver involvement
Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT) Activated
Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving
anticoagulant therapy, then as long as PT or PTT is within therapeutic range of
intended use of anticoagulants

- 1.5 X ULN unless subject is receiving anticoagulant therapy, then as long as PT
or PTT is within therapeutic range of intended use of anticoagulants * Hemoglobin
and platelet requirements cannot be met by use of recent transfusion or growth
factor support (GCSF or erythropoietin) within 2 weeks prior to treatment
initiation.

- Creatinine clearance should be calculated per institutional standard.

- Female subject of childbearing potential should have a negative urine
or serum pregnancy within 72 hours prior to receiving the first dose of
study medication. If the urine test is positive or cannot be confirmed
as negative, a serum pregnancy test will be required.

Female subjects of childbearing potential should be willing to use 2 methods of birth
control or be surgically sterile, or abstain from sexual activity for the course of the
study through 120 days after the last dose of study medication (Reference Section 5.7.2).
Subjects of child bearing potential are those who have not been surgically sterilized or
have not been free from menses for > 1 year.

Note: Abstinence is acceptable if this is the established and preferred contraception for
the subject.

- Male subjects should agree to use an adequate method of contraception starting with
the first dose of study therapy through 120 days after the last dose of study therapy.

Note: Abstinence is acceptable if this is the established and preferred contraception for
the subject.

Exclusion Criteria:

- Ann Arbor Stage III or IV disease at diagnosis or at relapse/refractory disease
confirmation.

- Bulky disease (>10cm) at diagnosis or at relapse/refractory disease confirmation.

- Active B symptoms.

- Received >1 line of therapy for Hodgkin lymphoma

- Relapsed/refractory disease within a prior radiation field.

- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
within 2 weeks prior to study Day 1 or who has not recovered (i.e. ≤ Grade 1 or at
baseline) from adverse events due to a previously administered agent.

- Diagnosis of immunosuppression or is receiving systemic steroid therapy or any other
form of immunosuppressive therapy within 7 days prior to the first dose of trial
treatment. The use of physiologic doses of corticosteroids may be approved after
consultation with the Sponsor.

- Has a known additional malignancy that is progressing or requires active treatment.
Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
skin, or in situ cervical cancer that has undergone potentially curative therapy.

- Has active autoimmune disease that has required systemic treatment in past 2 years
(i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). 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

- Has history of (non-infectious) pneumonitis that required steroids, evidence of
interstitial lung disease or active, non infectious pneumonitis

- Has an active infection requiring intravenous systemic therapy.

- Has a known Human Immunodeficiency Virus (HIV), Hepatitis B (HBV), or Hepatitis C
(HCV) infection

- Has received a live vaccine within 30 days prior to first dose

- Any other medical condition or laboratory evaluation that, in the treating physician's
or principal investigator's opinion, makes the patient unsuitable to participate in
this clinical trial

- Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not
recovered (i.e. ≤ Grade 1 or at baseline) from adverse events due to agents
administered more than 4 weeks earlier.

- Has had treatment a prior monoclonal antibody targeting PD-1, PD-L1, PD-L2, or CTLA-4.

- Has a pre-treatment TTE showing a calculated left ventricular ejection fraction of
less than 50%

- Has a pre-treatment PFT showing an DLCO adjusted for hemoglobin of less than 60%

- Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the pre-screening or screening visit
through 120 days after the last dose of trial treatment.