PET Adapted Brentuximab Vedotin and Pembrolizumab in Combination With Doxorubicin and Dacarbazine in Classic Hodgkin Lymphoma

Exclusion Criteria

• •1. Nodular lymphocyte predominant HL.
• •2. History of another malignancy within 3 years before the first dose of study drug or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk of metastasis or death (e.g., 5-year OS ≥90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer. Subjects 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 (e.g., immunoglobulin replacement, other monoclonal antibody therapies) within 4 weeks of first study drug dose, unless underlying disease has progressed on treatment.
• •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, including signs or symptoms of progressive multifocal leukoencephalopathy (PML) or history of PML. Subjects with a history of cerebral/meningeal disease related to the underlying malignancy are allowed if prior CNS disease has been treated.
• •6. Any active Grade 3 or higher (per the National Cancer Institute's Common Terminology Criteria for Adverse Events \[NCI CTCAE\] Version 4.03) viral, bacterial, or fungal infection within 1 week prior to the first dose of study drug. Routine antimicrobial prophylaxis is permitted.
• •7. Current therapy with other systemic anti-neoplastic or investigational agents.
• •8. Planned consolidative radiotherapy.
• •9. Active interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
• •10. Grade 3 or higher pulmonary disease unrelated to underlying malignancy.
• •11. Idiopathic interstitial pneumonia or diffusing capacity of the lung for carbon monoxide (adjusted for hemoglobin) \<50% predicted.
• •12. Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association Class III-IV within 6 months prior to their first dose of brentuximab vedotin. See Appendix E
• •13. Subjects with Child-Pugh class B or C hepatic impairment.
• •14. Other serious underlying medical condition that, in the opinion of the investigator, would impair the subject's ability to receive or tolerate the planned treatment and follow-up.
• •15. Symptomatic neurologic disease compromising normal activities of daily living or requiring medications. See Appendix G
• •16. Grade 2 or higher peripheral sensory or motor neuropathy at baseline.
• •17. Left ventricular ejection fraction \<45% or symptomatic cardiac disease (including symptomatic ventricular dysfunction, symptomatic coronary artery disease, and symptomatic arrhythmias), or previous treatment with complete cumulative doses of doxorubicin or other anthracyclines.
• •18. Subjects with acute or chronic graft-versus-host-disease (GvHD) or receiving immunosuppressive therapy as treatment for or prophylaxis agent against GvHD.
• •19. Previous treatment with brentuximab vedotin.
• •20. Known history of hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection.
• •21. Known to be positive for human immunodeficiency virus (HIV).
• •22. Subjects who are pregnant or breastfeeding.
• •23. Known hypersensitivity to any excipient contained in the drug formulation of brentuximab vedotin, any component of AD, pembrolizumab, doxorubicin, dacarbazine, filgrastim, or pegfilgrastim.
• •24. Treatment with botanical preparations (e.g., herbal supplements, traditional Chinese medicines) intended to treat the disease under study within 2 weeks prior to treatment.
• •25. Subjects who have received a live or attenuated vaccine within 30 days prior to treatment.
• •26. Subjects with an active autoimmune disease or any other condition requiring systemic treatment with either corticosteroids within 7 days (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 30 days of starting treatment. Inhaled or topical steroids, and adrenal replacement steroid doses \>10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease. a. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• •27. Subjects who received organ transplant or allogeneic stem cell transplantation.