A Phase III, Randomized Study of Nivolumab (Opdivo) Plus AVD or Brentuximab Vedotin (Adcetris) Plus AVD in Patients (Age >/= 12 Years) With Newly Diagnosed Advanced Stage Classical Hodgkin Lymphoma


This randomized phase III trial compares immunotherapy drugs (nivolumab or brentuximab vedotin) when given with combination chemotherapy in treating patients with newly diagnosed stage III or IV classic Hodgkin lymphoma. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Brentuximab vedotin is a monoclonal antibody, brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to cancer cells in a targeted way and delivers vedotin to kill them. Drugs used in chemotherapy, such as doxorubicin, vinblastine, and dacarbazine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. The addition of nivolumab or brentuximab vedotin to combination chemotherapy may shrink the cancer or extend the time without disease symptoms coming back.

Study Arms

  • Experimental: Arm I (chemotherapy, nivolumab, radiation)
  • Experimental: Arm II (chemotherapy, brentuximab vedotin, radiation)


  • All patients must have histologically confirmed newly diagnosed, previously untreated stage III or IV classical Hodgkin lymphoma (nodular sclerosing, mixed cellularity, lymphocyte-rich, or lymphocyte-depleted, or not otherwise specified [NOS]). Nodular lymphocyte predominant Hodgkin lymphoma is not eligible.
  • Patients must have bidimensionally measurable disease (at least one lesion with longest diameter >= 1.5 cm) documented on the Lymphoma Baseline Tumor Assessment Form in Rave.
  • Patients must have a whole body or limited whole body PET-CT scan performed within 42 days prior to registration. (A contrast-enhanced [diagnostic] CT, magnetic resonance imaging [MRI] or MRI-PET is acceptable in event that PET-CT is contraindicated, however the same modality must be utilized through the trial.) NOTE: All images from PET-CT, CT, MRI or MR-PET scans performed as standard of care to assess disease (within 42 days prior to registration) must be submitted and associated radiology reports must be submitted.
  • Patients must not have received any prior chemotherapy, radiation, or antibody-based treatment for classical Hodgkin lymphoma. Steroid pre-treatment is permitted.
  • Patients must not have had prior solid organ transplant.
  • Patients must not have had prior allogeneic stem cell transplantation.
  • Patients must not have received a live vaccine within 30 days prior to planned day 1 of protocol therapy (e.g. measles, mumps, rubella, varicella, yellow fever, rabies, Bacillus Calmette-Guerin [BCG], oral polio vaccine, and oral typhoid).
  • At registration, investigator must declare intent-to-treat with residual PET radiation therapy (residual PET RT- RPRT) to be administered after patient completes 6 cycles of therapy if, after end of treatment, the patient meets criteria specified for receiving RT). Patients will be stratified by investigator's intent-to-treat with residual PET RT.
    • All patients enrolled by Children's Oncology Group (COG) investigators will be considered intent-to-treat with residual PET RT.
  • Patients must have a performance status corresponding to Zubrod scores of 0, 1 or 2. Use Lansky for patients =< 17 years of age. *The conversion of the Lansky to Eastern Cooperative Oncology Group (ECOG) scales is intended for National Cancer Institute (NCI) reporting purposes only.
  • Adults (age 18 or older): Creatinine clearance >= 30 mL/min, as estimated by the Cockcroft and Gault formula. The creatinine value used in the calculation must have been obtained within 28 days prior to registration. Estimated creatinine clearance is based on actual body weight.