AMC 120, Glofitamab Plus Chemoimmunotherapy in Newly Diagnosed HIV-Associated Large B-Cell Lymphoma (The "Glofit-RCHOP Study")

PRIMARY OBJECTIVE: I. To establish the feasibility and safety of the regimen glofitamab plus rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (Glofit-RCHOP) in people with newly diagnosed Human Immunodeficiency Virus (HIV)-associated large B-cell lymphoma (LBCL). SECONDARY OBJECTIVES: I. To evaluate the toxicity of Glofit-RCHOP when utilized in combination with antiretroviral therapy (ART) as assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. II. To evaluate the overall response rate (ORR) and complete response rate (CRR) for Glofit-RCHOP in newly diagnosed HIV-associated LBCL using Lugano criteria. III. To evaluate progression-free survival (PFS), duration of response (DoR), and overall survival (OS) for Glofit-RCHOP in newly diagnosed HIV-associated LBCL. EXPLORATORY OBJECTIVES: I. To prospectively assess if circulating tumor deoxyribonucleic acid (ctDNA) levels at baseline and ctDNA dynamics (e.g., changes in ctDNA levels after 3 cycles and at end of treatment) can predict outcomes of therapy (PFS and OS). II. To characterize the genetic subtypes of newly diagnosed HIV-associated LBCL based on commonly occurring genetic alterations. III. To assess dynamic changes in cluster of differentiation 4 (CD4) and cluster of differentiation 8 (CD8) counts during treatment with Glofit-RCHOP. IV. To assess the relationship between T-cell subsets, serum levels of cytokines, and inflammation-associated/microbial-translocation molecular profiles with clinical response in HIV-associated aggressive B-cell lymphomas treated with Glofit-RCHOP. V. To assess the impact of Glofit-RCHOP on quality of life (QoL). VI. To assess the prognostic significance of myelocytomatosis oncogene (MYC) overexpression (defined as MYC immunohistochemistry \[IHC\] ≥ 40%). VII. To assess the association of HIV viral load prior to starting glofitamab on frequency and severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). OUTLINE: Patients receive RCHOP consisting of: rituximab intravenously (IV) over 90-360 minutes, cyclophosphamide IV over 1 hour, doxorubicin IV over 3-10 minutes, and vincristine IV over 3-10 minutes on day 1 of each cycle, and prednisone orally (PO) once daily (QD) on days 1-5 of each cycle. Patients also receive glofitamab IV over 4 hours on days 8 and 15 of cycle 2 and on day 8 of cycles thereafter. Cycles of RCHOP repeat every 21 days for 6 cycles, and cycles of glofitamab repeat every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo echocardiogram (ECHO), bone marrow biopsy or aspiration, positron emission tomography/computed tomography (PET/CT), and blood sample collection throughout the study. Patients may also undergo tumor tissue biopsy during screening. After completion of study treatment, patients are followed every 3 months.