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....
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) in PLWH, which portends a poorer prognosis, than in the general population. * Plasmablastic lymphoma (PBL) is a rare CD20 negative B cell lymphoma associated with EBV almost exclusively seen in PLWH. * Although these subtypes of lymphoma occur in the general population, their presentation and pathogenesis may be different - meaning there may be different therapeutic targets and strategies to consider in HIV-associated lymphomas necessitating clinical trials targeted to this underserved population of patients. * Lenalidomide, a 2nd generation immunomodulatory drug, has shown safety and improved survival in combination with chemotherapy in advanced stage DLBCL in one of two randomized trials. * Pomalidomide, a 3rd generation immunomodulatory agent, has activity in primary central nervous system (CNS) lymphoma demonstrating its activity in both NHL and CNS involvement, which is more common in PLWH and NHL. In a number of parameters, it is more potent than lenalidomide. * Pomalidomide has shown to increase natural killer (NK) and T-cell activation and reverse T-cell senescence in addition to increasing CD4+ T-cell count in PLWH and cancer. It can also enhance expression of surface immune markers in vitro in cell lines from EBV-induced tumors. * Dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH) along with rituximab (DA-EPOCH-R) is an anthracycline-based regimen that has been shown to be safe and effective in PLWH and in the most common subtypes of NHL seen in PLWH, DLBCL and BL. Objective: -Determine the safety and maximum tolerated dose (MTD) of the combination of pomalidomide and dose-adjusted EPOCH +/ rituximab (DA-EPOCH-RP) in participants with enrolled subtypes of HIV-associated lymphomas Eligibility: * Adult participants \>= 18 years with pathology-confirmed HIV-associated B-cell non-Hodgkin lymphoma with high-risk features, excluding primary CNS lymphoma * Positive HIV1/2 serology Design: * This is a phase 1 study of DA-EPOCH-RP in participants with HIV-associated B-cell non-Hodgkin lymphoma. Only participants with CD20+ HIV-associated B-cell non-Hodgkin lymphoma will receive Rituximab. * This is a dose escalation study to evaluate pomalidomide in combination with modified DA-EPOCH-R to determine safety and tolerability. Dosing will begin at dose level 1, 3 mg of pomalidomide and proceed to dose escalation or de-escalation to doses 4 mg or 2 mg depending on dose-limiting toxicities. * Participants will be prescribed ART. * In this phase I study, up to 12 evaluable participants will be accrued in the escalation phase (3-6 participants per level) and up to 6 evaluable participants will be accrued in the expansion phase to be treated at MTD.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
25
0.4 mg/m2/day administered by CIVI on days 1 to 4
60 mg/m2/day administered orally on days 1 to 5
10 mg/m2/day administered by CIVI on days 1 to 4
50 mg/m2/day administered by CIVI on days 1 to 4
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.
750 mg/m2 administered IV on day 5
375 mg/m2 administered IV on day 1 (only for CD20+ tumors)
National Institutes of Health Clinical Center
Bethesda, Maryland, United States
RECRUITINGsafety and tolerability
The fraction of individuals with toxicity noted at each dose level will be reported by grade and type of toxicity identified. Maximum tolerated dose will also be reported.
Time frame: 6 cycles of treatment, or until confirmed progression, unacceptable toxicity or trial withdrawal
progression-free survival
duration of time from the start of the treatment until time of disease relapse from PR, disease progression, or death, whichever occurs first
Time frame: every 3 weeks for the first 6 cycles, every 3 months for the rest of the first year, then every 6 months for 4 years (5 years total).
preliminary estimates of response
Percentage of individuals with the best overall response of CR or PR to therapy
Time frame: every 3 weeks for the first 6 cycles, every 3 months for the rest of the first year, then every 6 months for 4 years (5 years total).
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