Clinical Trial of Brentuximab Vedotin in Classical Hodgkin Lymphoma

Inclusion Criteria

Treatment-naïve, classic Hodgkin lymphoma (cHL) participants

1. Participants enrolling in Part A of the study must have Ann Arbor Stage III or IV disease
2. Participants enrolling in Part B of the study must have Ann Arbor Stage I or II cH: with bulky mediastinal disease, or Stage III or IV
3. Participants enrolling in Part C of the study must have Ann Arbor Stage I or II cHL without bulky disease
4. Histologically confirmed cHL according to the current World Health Organization (WHO) Classification
5. Bidimensional measurable disease as documented by PET/CT or CT imaging
6. Age 12 years or older in the United States. For regions outside of the US, participants must 18 years or older.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

Exclusion Criteria

1. Nodular lymphocyte predominant HL
2. History of another malignancy within 3 years of the first dose of study drug or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk or metastasis or death. Participants with nonmelanoma skin cancer, localized prostate cancer, or carcinoma in situ of any type are not excluded if they have undergone complete resection
3. Prior immunosuppressive chemotherapy, therapeutic radiation, or any immunotherapy within 4 weeks of the first study drug dose
4. Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
5. Active cerebral/meningeal disease related to the underlying malignancy
6. Any active Grade 3 or higher viral, bacterial, or fungal infection within two weeks of the first dose of study drug (Grade 3 defined by the National Cancer Institute's Common Terminology Criteria for Adverse Events, NCI CTCAE Version 4.03)
7. Current therapy with other systemic anti-neoplastic or investigational agents
8. Planned consolidative radiotherapy (Parts B and C only)
9. Active interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity (Parts B and C only)
10. Grade 3 or higher pulmonary disease unrelated to underlying malignancy
11. Documented history of idiopathic interstitial pneumonia or diffusing capacity of the lung for carbon monoxide <50% predicted
12. History of a cerebral vascular event within 6 months of first dose of study drug
13. Child-Pugh B or C hepatic impairment
14. Grade 2 or higher peripheral sensory or motor neuropathy
15. Participants with acute or chronic graft-versus-host-disease (GvHD) or receiving immunosuppressive therapy as treatment or as prophylaxis against GvHD
16. Previous treatment with brentuximab vedotin
17. Participants who are pregnant or breastfeeding
18. Other serious condition that would impair the participant's ability to receive or tolerate the planned treatment and follow-up