This partially randomized phase I/II trial studies the side effects and the best dose of vorinostat when given together with combination chemotherapy and rituximab to see how well it works compared to combination chemotherapy alone in treating patients with human immunodeficiency virus-related diffuse large B-cell non-Hodgkin lymphoma or other aggressive B-cell lymphomas. Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as rituximab, may interfere with the ability of cancer cells to grow and spread. Giving vorinostat together with combination chemotherapy and rituximab may kill more cancer cells.
A Sequential Phase I/Randomized Phase II Trial of Vorinostat and Risk-Adapted Chemotherapy With Rituximab in HIV-Related B-cell Non-Hodgkin's Lymphoma
I. Determine the recommended phase II dose (RPTD) of vorinostat that may be used in combination with dose-adjusted etoposide, prednisone, vincristine sulfate, cyclophosphamide, doxorubicin hydrochloride and rituximab (R-DA-EPOCH) (in high-risk disease) in participants with human immunodeficiency virus (HIV)-associated aggressive cluster of differentiation (CD)20 positive non-Hodgkin lymphoma (NHL). (Phase I) II. Determine the overall toxicity rates of R-DA-EPOCH (in high-risk disease) with and without vorinostat. (Phase II) III. Determine the efficacy of the combinations of R-DA-EPOCH (in high-risk disease) with and without vorinostat in HIV-associated aggressive CD20 positive NHL using complete response (CR) rates as study endpoints. (Phase II)
I. Determine 1-year event-free survival (EFS) and 1 year overall survival (OS). II. Assess the effect of vorinostat and chemotherapy on latent HIV in memory T cells.
III. Assess the effect of vorinostat and/or chemotherapy on HIV, Epstein-Barr virus (EBV), and human herpes virus 8 (HHV-8) viral loads on banked specimens.
IV. Assess the effect of vorinostat and/or chemotherapy on T-cell subsets (CD4 and CD8) and plasma immunoglobulin levels.
V. Assess the effect of concurrent vorinostat and rituximab on plasma steady-state concentrations of etoposide, doxorubicin (doxorubicin hydrochloride), and vincristine (vincristine sulfate) (on Phase I only).
VI. Perform wide human gene expression profiling and methylation studies in tumors banked at baseline.
VII. Evaluate EBV and HHV-8 gene expression patterns in positive tumors banked at baseline.
OUTLINE: This is a phase I, dose-escalation study of vorinostat followed by a phase II study.
PHASE I: Patients receive vorinostat orally (PO) once daily (QD) on days 1-5; rituximab intravenously (IV) on day 1; etoposide IV over 24 hours, doxorubicin hydrochloride IV over 24 hours, and vincristine sulfate IV over 24 hours on days 1-4; prednisone PO daily on days 1-5; and cyclophosphamide IV over 1 hour on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
PHASE II: Patients are randomized to 1 of 2 treatment arms.
ARM A (VR-DA-EPOCH): Patients receive vorinostat, rituximab, etoposide, doxorubicin hydrochloride, vincristine sulfate, prednisone, and cyclophosphamide as in Phase I.
ARM B (DA-R-EPOCH): Patients receive rituximab, etoposide, doxorubicin hydrochloride, vincristine sulfate, prednisone, and cyclophosphamide as in Arm A.
In all arms, treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
AIDS-Related Diffuse Large Cell Lymphoma AIDS-Related Plasmablastic Lymphoma AIDS-Related Primary Effusion Lymphoma Grade 3b Follicular Lymphoma HIV Infection Plasmablastic Lymphoma Primary Effusion Lymphoma Recurrent Adult Diffuse Large Cell Lymphoma Recurrent Grade 3 Follicular Lymphoma Stage I Adult Diffuse Large Cell Lymphoma Stage I Grade 3 Follicular Lymphoma Stage II Contiguous Adult Diffuse Large Cell Lymphoma Stage II Grade 3 Contiguous Follicular Lymphoma Stage II Grade 3 Non-Contiguous Follicular Lymphoma Stage II Non-Contiguous Adult Diffuse Large Cell Lymphoma Stage III Adult Diffuse Large Cell Lymphoma Stage III Grade 3 Follicular Lymphoma Stage IV Adult Diffuse Large Cell Lymphoma Stage IV Grade 3 Follicular Lymphoma Cyclophosphamide Rituximab Liposomal doxorubicin Etoposide phosphate Vorinostat Doxorubicin Prednisone Etoposide Vincristine Podophyllotoxin Antibodies Immunoglobulins Antibodies, Monoclonal Cortisone acetate Cortisone
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