The overall goal of this study is to compare the effects, good and/or bad of the study drugs brentuximab vedotin and nivolumab (Bv-NIVO) against the standard therapy of chemotherapy with or without radiation for people with Hodgkin Lymphoma (HL) to find out which is better.

Treatment with brentuximab vedotin and nivolumab (Bv-NIVO) is considered investigational, which means it has not yet been approved by the U.S. Food and Drug Administration (FDA).

The first part of treatment in this study involves cancer fighting medicine called chemotherapy. A commonly used chemotherapy combination called ABVD will be administered via in intravenous infusion (IV) for 2 cycles. This part of the study takes approximately 2 months.

Based on how the cancer responds to the first part of therapy, the study doctors will find out if each participant has a rapid early response (RER) or a slow early response (SER) to treatment. In addition to the response to the initial therapy, they will use known risk factors, called favorable or unfavorable, to help decide the next part of therapy. Favorable risk means the cancer is less likely to come back after treatment while unfavorable risk means the cancer has a greater chance of coming back.

Regardless of response or risk, the treatment plan that all participants receive after initial ABVD therapy is decided by a process called randomization. Randomization means that the treatment is assigned based on chance. It is a lot like flipping a coin, except that it is done by computer.

For patients with RER to initial ABVD treatment: 
RER means the cancer responded quickly to the ABVD and the results of tests show that the cancer has gone into remission very soon after the start of treatment. Remission is a disappearance of signs and symptoms of active cancer.

Treatment for RER participants after initial ABVD therapy involves standard chemotherapy or Bv-NIVO. This group will receive another 2 to 4 months of treatment after initial ABVD therapy.

Those with RER will receive 1 of 2 treatment plans, depending on whether the cancer has favorable or unfavorable risk factors. Participants with favorable risk factors will receive either the standard therapy for favorable Hodgkin Lymphoma or the investigational therapy with Bv-NIVO. Participants with unfavorable risk factors will be assigned to receive either the standard therapy for unfavorable HL or investigational therapy with Bv-NIVO. 

For patients with SER to initial ABVD treatment: 
SER means your cancer responds to treatment more slowly and takes longer to reach remission. Once remission is reached, more therapy is needed to maintain that remission.

Treatment for SER participants after initial ABVD therapy involves standard chemotherapy or Bv-NIVO. Participants will also receive radiation therapy (the use of strong x-rays to kill cancer cells) to the area(s) that is affected by Hodgkin Lymphoma after the last dose of the study drug. This group will receive another 3 to 5 months of treatment after initial ABVD therapy.

Those with SER will get 1 of 2 treatment plans. Participants with favorable or unfavorable risk factors may get either the standard therapy for those with slow response to initial therapy or investigational therapy with Bv-NIVO.