A Study of Daratumumab and Dose-Adjusted EPOCH in Plasmablastic Lymphoma

PRIMARY OBJECTIVES: 1\. To evaluate the feasibility of adding daratumumab to DA-EPOCH by assessing the percentage of PBL patients who complete ≥3 cycles of study treatment per protocol. SECONDARY OBJECTIVES: 1. To estimate the complete response (CR) rate as defined by the 2017 RECIL Criteria in HIV positive and HIV negative patients with plasmablastic lymphoma treated with daratumumab and DA-EPOCH. 2. To evaluate the safety of dose-adjusted EPOCH with daratumumab as assessed by the NCI CTCAE version 5.0. 3. To estimate the overall survival (OS), progression free survival (PFS), and event free survival (EFS) at 1 year. EXPLORATORY OBJECTIVES: 1. To explore the relationship of tumor characteristics as determined by immunohistochemistry (IHC) panels and fluorescent in situ hybridization (FISH) and clinical outcomes. 2. To assess the relationship between EBV-tumor association and EBV plasma copy number and to assess any prognostic significance of clearance of viral DNA from plasma during or at the end of therapy 3. To determine the feasibility of identifying circulating tumor DNA (ctDNA) as reflected in plasma DNA mutation panels or clonal immunoglobulin DNA and to and to assess any prognostic significance of clearance of tumor DNA from plasma during therapy. OUTLINE: Patients receive daratumumab intravenously (IV) on days 1 (± 3 days), 8 (± 2 days), and 15 (± 2 days) of cycles 1-3, and on day 1 of cycles 4-6. Patients also receive etoposide, doxorubicin hydrochloride, and vincristine sulfate IV continuous over 96 hours on days 1-4, prednisone orally (PO) on days 1-5, and cyclophosphamide IV over 1 hour on day 5. Treatment repeats every 21 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 up to 2 years.