HIV Infection Clinical Trial
Official title:
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
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.
PRIMARY OBJECTIVES: 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) SECONDARY OBJECTIVES: 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 5. 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. ;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Active, not recruiting |
NCT02135419 -
Treatment in Preventing Anal Cancer in Patients With HIV and Anal High-Grade Lesions
|
Phase 3 | |
| Active, not recruiting |
NCT02663856 -
My Smart Age With HIV: Smartphone Self-assessment of Frailty
|
||
| Terminated |
NCT02743598 -
Liraglutide for HIV-associated Neurocognitive Disorder
|
Phase 4 | |
| Completed |
NCT02659306 -
Metformin Immunotherapy in HIV Infection
|
Phase 1 | |
| Completed |
NCT02921516 -
Growing Up: Intervening With HIV-Positive Adolescents in Resource-Poor Settings
|
N/A | |
| Completed |
NCT02663869 -
Aging With HIV at Younger vs Older Age: a Diverse Population With Distinct Comorbidity Profiles
|
||
| Completed |
NCT02846402 -
Impact of HIV Self-testing Among Female Sex Workers in Kampala, Uganda
|
N/A | |
| Completed |
NCT02564341 -
Targeting Effective Analgesia in Clinics for HIV - Intervention
|
N/A | |
| Active, not recruiting |
NCT02302950 -
A Retrospective Analysis of Raltegravir Use in Minority HIV Infected Women in Houston, Texas
|
N/A | |
| Completed |
NCT01830595 -
Lactoferrin Treatment in HIV Patients
|
Phase 2 | |
| Terminated |
NCT01902186 -
Bone Mineral Density Changes in HIV-positive Females With Osteopenia Switching to Raltegravir
|
Phase 4 | |
| Terminated |
NCT02109224 -
Ibrutinib in Treating Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma in Patients With HIV Infection
|
Phase 1 | |
| Completed |
NCT02269605 -
Bryostatin-1 Effect on HIV-1 Latency and Reservoir in HIV-1 Infected Patients Receiving Antiretroviral Treatment
|
Phase 1 | |
| Completed |
NCT01852942 -
Reversing Tissue Fibrosis to Improve Immune Reconstitution in HIV
|
Phase 2 | |
| Completed |
NCT01946217 -
Factors Affecting Patient Participation in AIDS Malignancy Clinical Trials Consortium Clinical Trials
|
N/A | |
| Completed |
NCT02527135 -
Text Messaging to Improve HIV Testing Among Young Women in Kenya
|
N/A | |
| Completed |
NCT02525146 -
Birmingham Access to Care Study
|
N/A | |
| Completed |
NCT02118168 -
Observational Study for the Extended Follow-up of the Patients Enrolled in the Therapeutic Clinical Trial ISS T-002
|
N/A | |
| Active, not recruiting |
NCT02602418 -
Neural Correlates of Working Memory Training for HIV Patients
|
N/A | |
| Completed |
NCT01680094 -
Safety and Effect of The HDAC Inhibitor Panobinostat on HIV-1 Expression in Patients on Suppressive HAART
|
Phase 1/Phase 2 |