Limited stage Hodgkin lymphoma is a highly curable disease, but standard treatment with ABVD chemotherapy and radiation can lead to late risks of secondary cancers, lung injury, heart injury, and others. This trial eliminates radiation therapy and reduces intensity of chemotherapy by incorporating the highly active FDA-approved targeted therapy brentuximab vedotin, an antibody-drug conjugate specifically against the lymphoma cells, combined with the standard chemotherapy drugs Adriamycin and Dacarbazine (AD).

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied. It also means that the FDA (the U.S. Food and Drug Administration) has not yet approved brentuximab vedotin (brentuximab) as part of the initial treatment of Hodgkin lymphoma. Currently, brentuximab is FDA-approved for treatment of relapsed Hodgkin lymphoma.

• Brentuximab works by binding specifically to Hodgkin lymphoma cells, entering the cells, and then releasing the drug to destroy the cell.
• The chemotherapy drugs Adriamycin and Dacarbazine (AD) which which participants will receive in this research study are approved for use in people with Hodgkin Lymphoma.
• Patients will not receive planned radiation therapy, or the drugs bleomycin or vinblastine.

Inclusion Criteria:

• Previously untreated stage IA, IB, or IIA classical Hodgkin Lymphoma

• Non-bulky disease defined as less than 10 cm in maximal diameter

• Measurable disease ≥1.5 cm

• Age ≥18

• ECOG performance status 0-2 (see Appendix B)

• Participants must have initial organ and marrow function as defined below:

  • Absolute neutrophil count ≥ 1,000/mcL
  • Platelets ≥100,000/mcL
  • Total bilirubin ≤ 2, unless due to Gilbert's disease
  • AST (SGOT)/ALT (SGPT) ≤ 2.5 X institutional upper limit of normal
  • Creatinine clearance ≥ 30 mL/min

• LVEF by echocardiogram or MUGA within institutional normal limits

• Participant must be willing to use two effective forms of birth control during protocol therapy. Men and women must continue using two effective forms of birth control for 6 months following treatment.

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Participants who have had prior cHL-directed chemotherapy or radiotherapy
• Participants may not be receiving any other investigational agents
• Participants with known CNS involvement of lymphoma
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Adriamycin, Dacarbazine, or brentuximab
• Pre-existing grade 2 or greater neuropathy
• 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
• Pregnant women are excluded from this study because brentuximab is an antibody drug conjugate with a linked potent anti-tubule agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with brentuximab, breastfeeding should be discontinued if the mother is treated with brentuximab. These potential risks may also apply to other agents used in this study.
• Participants with a history of a different malignancy are ineligible unless they have been disease free for 1 year and considered at low risk for relapse, except for: cervical cancer in situ, ductal carcinoma in situ, localized prostate cancer with no detectable disease by imaging studies, and non-melanoma cancers of the skin, which are eligible at any time.
• Known HIV positivity

From the start of treatment until 30 days after the end of treatment (up to approximately 5 months)