Pembrolizumab and Involved Site Radiation Therapy in Treating Patients with Early Stage Relapsed or Refractory Hodgkin Lymphoma

Inclusion Criteria

• Three populations of patients are eligible for enrollment: * 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) * 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 * 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 at enrolling institution
• Age 12 or older
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 or Lansky performance status of ≥ 50 (patients [Pts] 12-15 years of age)
• Absolute neutrophil count (ANC) >= 1,000/mcL (within 14 days of treatment initiation)
• Platelets >= 75,000/mcL (within 14 days of treatment initiation) * Hemoglobin and platelet requirements cannot be met by use of recent transfusion or growth factor support (granulocyte-colony stimulating factor [GCSF] or erythropoietin) within 2 weeks prior to treatment initiation
• Hemoglobin >= 8g/dL (within 14 days of treatment initiation) * 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 =< 1.5 x upper limit of normal for age (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 60 mL/min for subject with creatinine levels > 1.5 x institutional ULN (within 14 days of treatment initiation) * Creatinine clearance should be calculated per institutional standard
• Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN (within 14 days of treatment initiation)
• Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT) alanine aminotransaminase (ALT) glutamate pyruvate transaminase (SGPT) =< 2.5 x ULN for age (within 14 days of treatment initiation)
• International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless subject is receiving anticoagulation therapy, then as long at PT or partial prothrombin time (PTT) is within therapeutic range of intended use of anticoagulants (within 14 days of treatment initiation)
• 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 (within 14 days of treatment initiation)
• 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; 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 (> 10 cm) 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 virus (HBV), or hepatitis C virus (HCV) infection
• Has received a live vaccine or live-attenuated vaccine within 30 days prior to first dose of study drug. Administration of killed vaccines is allowed.
• 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 transthoracic echocardiography (TTE) showing a calculated left ventricular ejection fraction of less than 50%
• Has a pre-treatment pulmonary function test (PFT) showing an carbon monoxide diffusing capability (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