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.
I. To compare the progression-free survival (PFS) in patients with newly diagnosed advanced
stage classical Hodgkin lymphoma randomized to N-AVD (nivolumab, doxorubicin hydrochloride
[doxorubicin], vinblastine sulfate [vinblastine], dacarbazine) versus that obtained with
BV-AVD (brentuximab vedotin, doxorubicin, vinblastine, dacarbazine).
I. To compare overall survival (OS) in patients randomized to N-AVD versus BV-AVD.
II. To compare event-free survival (EFS) in patients randomized to N-AVD versus BV-AVD.
III. To compare the metabolic complete response (CR) rate at the end of treatment in patients
randomized to N-AVD versus BV-AVD.
IV. To compare the physician-reported treatment-related adverse event rates between arms
stratified by age groups.
V. To compare patient-reported symptoms using selected Patient Reported Outcome Common
Toxicity Criteria for Adverse Events (PRO-CTCAE) items between arms stratified by age groups.
VI. To compare the safety and tolerability of N-AVD versus that of BV-AVD.
QUALITY OF LIFE OBJECTIVES:
I. To compare between arms patient-reported fatigue, neuropathy and health-related quality of
life over time (baseline, beginning of cycle 3, 4-8 weeks after completion of treatment, and
1 and 3 years after randomization) using the Patient Reported Outcomes Measurement
Information System (PROMIS)-Fatigue, the Functional Assessment of Cancer Therapy/Gynecologic
Oncology Group-Neurotoxicity (FACT/GOG-Ntx), and the PROMIS Global, respectively.
I. To bank specimens for future correlative studies. II. To bank positron emission tomography
(PET)-computed tomography (CT) images for future correlative studies.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive doxorubicin hydrochloride intravenously (IV), vinblastine sulfate IV,
dacarbazine IV, and nivolumab IV over 30 minutes on days 1 and 15. Patients may receive
pegfilgrastim subcutaneously (SC) on days 2 and 16, or filgrastim SC or IV on days 5-10 and
20-25 for adults or days 4-9 for pediatric patients. Treatment repeats every 28 days for 6
cycles in the absence of disease progression or unacceptable toxicity. After completion of
cycle 6, patients may receive radiation therapy 5 days per week for approximately 4 weeks at
the discretion of the treating physician.
ARM II: Patients receive doxorubicin hydrochloride IV, vinblastine sulfate IV, dacarbazine
IV, and brentuximab vedotin IV over 30 minutes on days 1 and 15. Patients may receive
pegfilgrastim SC on days 2 and 16, or filgrastim SC or IV on days 5-10 and 20-25 for adults
or days 4-9 for pediatric patients. Treatment repeats every 28 days for 6 cycles in the
absence of disease progression or unacceptable toxicity. After completion of cycle 6,
patients may receive radiation therapy 5 days per week for approximately 4 weeks at the
discretion of the treating physician.
After completion of study treatment and prior to disease progression, patients are followed
up every 3 months for the first year, every 6 months for years 2 and 3, then annually until
10 years after registration. Patients are followed up at the time of progression and then
annually until 10 years after registration. Patients who receive radiation therapy are
followed up at 8-12 weeks after completion of radiation therapy.
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
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