Trials / Recruiting

RecruitingNCT05389423

Pomalidomide and Dose-Adjusted EPOCH +/- Rituximab for HIV-Associated Lymphomas

Phase I Trial of Pomalidomide and Dose-Adjusted EPOCH +/- Rituximab for HIV-Associated Lymphomas

Status: Recruiting
Phase: Phase 1
Study type: Interventional
Enrollment: 25 (estimated)

Sponsor: National Cancer Institute (NCI) · NIH
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

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....

Detailed 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) 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.

Conditions

Interventions

Type	Name	Description
DRUG	Vincristine	0.4 mg/m2/day administered by CIVI on days 1 to 4
DRUG	Prednisone	60 mg/m2/day administered orally on days 1 to 5
DRUG	Doxorubicin	10 mg/m2/day administered by CIVI on days 1 to 4
DRUG	Etoposide	50 mg/m2/day administered by CIVI on days 1 to 4
DRUG	Pomalidomide	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.
DRUG	Cyclophosphamide	750 mg/m2 administered IV on day 5
DRUG	Rituximab	375 mg/m2 administered IV on day 1 (only for CD20+ tumors)

Timeline

Start date: 2023-06-27
Primary completion: 2028-06-01
Completion: 2032-06-01
First posted: 2022-05-25
Last updated: 2026-02-19

Locations

1 site across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT05389423. Inclusion in this directory is not an endorsement.