Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With Stage II-IV HIV-Associated Hodgkin Lymphoma

PRIMARY OBJECTIVES I. To identify the maximum tolerated dose (MTD) of brentuximab vedotin when combined with the doxorubicin hydrochloride, vinblastine sulfate, and dacarbazine (AVD) chemotherapy regimen in the treatment of HIV-associated stage II-IV Hodgkin lymphoma. (Phase I) II. Establish an estimate of the two-year progression-free survival (PFS) for participants with HIV-associated stage II-IV Hodgkin lymphoma when treated using brentuximab vedotin plus the AVD chemotherapy regimen. (Phase II) SECONDARY OBJECTIVES: I. To evaluate the toxicity of AVD and brentuximab vedotin with highly active antiretroviral therapy (HAART). II. To estimate the partial response (PR) rate, complete response (CR) rate, overall survival (OS), and event free survival (EFS) at 2 and 5 years. III. To evaluate the effect of AVD and brentuximab vedotin on cluster of differentiation (CD)4 and CD8 counts after cycle 1, 4, at the end of therapy, and every 3 months after treatment completion for one year. IV. To investigate the prognostic value of fludeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) scans at baseline, after cycle 2, and at treatment completion, with respect to 2-year progression free survival. V. To evaluate HAART status at baseline and to correlate this with tumor response to therapy and OS and PFS. VI. To characterize the histologic subtypes in HIV-Hodgkin lymphoma (HL) in the highly active antiretroviral therapy (HAART) era. VII. To assess the neurotoxicity of HAART in combination with AVD and brentuximab vedotin. VIII. To evaluate effect of AVD and brentuximab vedotin on viral load after cycles 1, 4, at the completion of therapy, and every 3 months after treatment completion for one year. IX. To perform pharmacokinetic and immunogenicity studies to determine drug levels during therapy. X. To perform micro ribonucleic acid (miRNA) profile analysis on the HIV-HL tumor specimens and to correlate miRNA expression with OS, PFS, tumor response to therapy, histologic subtype of HIV-HL, and HIV disease characteristics. XI. To perform tissue microarray analysis on HIV-HL tumor specimens and to correlate the markers studied with OS, PFS, and tumor response to therapy. XII. To identify Epstein-Barr virus (EBV)-associated tumor derived deoxyribonucleic acid (DNA) in the plasma of study participants and to correlate these levels during therapy with disease response and OS. (Phase II) XIII. To identify cytokines in the plasma of participants during therapy that can be used as tumor and prognostic markers. (Phase II) XIV. To assess latent and expressed HIV reservoirs before, during, and post chemotherapy. To understand how cytotoxic chemotherapeutic agents affect HIV expression. OUTLINE: This is a phase I, dose-escalation study of brentuximab vedotin followed by a phase II study. Patients receive doxorubicin hydrochloride intravenously (IV), vinblastine sulfate IV, and dacarbazine IV on days 1 and 15. Patients also receive brentuximab vedotin IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.