Phase I Trial of Pomalidomide and Dose-Adjusted EPOCH +/- Rituximab for HIV-Associated Lymphomas
National Cancer Institute (NCI)
Summary
Background: Non-Hodgkin lymphoma (NHL) is the most common cancer among people living with HIV in the United States. People with HIV are up to 17 times more likely to get NHL than people who do not have HIV. The disease may also be different in these two groups. More study is needed for treating people with both HIV and NHL. Objective: To test a study drug (pomalidomide) in combination with chemotherapy with or without another drug (rituximab) in people with HIV-associated NHL. Eligibility: Adults aged 18 years or older diagnosed with HIV-associated B-cell NHL with high-risk features. Design: Individuals will undergo screening. They will have a physical exam. They will have blood and urine tests and tests of heart function. They may have imaging scans. Researchers will review tissue samples of individual s tumors. In some cases, a new biopsy may be needed. Individuals will receive up to 6 cycles of treatment. The first cycle is 26 days: Individuals will take pomalidomide by mouth for 10 days. After 5 days they will start receiving chemotherapy drugs through a tube attached to a needle placed in a vein (IV). Some participants will receive rituximab on day 5. All individuals will receive a second set of IV drugs that will last for 4 days (96 hours). They will receive another IV drug after the previous treatment is complete. The remaining cycles are each 21 days. Individuals will take pomalidomide by mouth for the first 10 days. Other chemotherapy treatments will also be repeated starting on day 1 of each cycle. Screening tests will be repeated at study visits. Follow-up visits will continue for 4 years....
Description
Background: * Non-Hodgkin lymphoma (NHL) is the most common cancer among people living with human immunodeficiency virus (HIV) (PLWH) in the United States. Even in the modern era of antiretroviral therapy (ART), PLWH have an 11- to 17-fold higher risk of NHL than the general population due in part to CD4+ T-cell lymphopenia but also immune dysregulation and exhaustion from chronic viral antigen stimulation. * The most common NHL subtypes are diffuse large cell lymphoma (DLBCL) and Burkitt lymphoma (BL), that are much more frequently associated with the oncogenic virus Epstein Barr virus (EBV)…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
* INCLUSION CRITERIA: * Histologically or cytologically confirmed B-cell NHL confirmed by the Laboratory of Pathology (LP), NCI, with one or more of the following features: * Leptomeningeal/CSF involvement * High-risk for CNS relapse per CNS-IPI (score 4-6) * Plasmablastic histology * Gamma herpesvirus positive tumor * Presence of KS * Measurable or evaluable lymphoma. * Positive HIV1/2 serology. * Individuals may not have received prior curative-intent chemotherapy for lymphoma. Individuals who have received prior treatment as a bridge to curative-intent therapy will be considered…
Interventions
- DrugVincristine
0.4 mg/m2/day administered by CIVI on days 1 to 4
- DrugPrednisone
60 mg/m2/day administered orally on days 1 to 5
- DrugDoxorubicin
10 mg/m2/day administered by CIVI on days 1 to 4
- DrugEtoposide
50 mg/m2/day administered by CIVI on days 1 to 4
- DrugPomalidomide
An initial dose of 3mg administered orally for 10 days in all cycles. In cycle 1, it will start 5 days before DA-EPOCH; in cycles 2-6, it will start on day 1. Administered at an MTD dose for the expansion phase.
- DrugCyclophosphamide
750 mg/m2 administered IV on day 5
- Drug
Location
- National Institutes of Health Clinical CenterBethesda, Maryland