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

Non-Hodgkin Lymphoma Clinical Trial

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

Status Recruiting

Clinical Trial 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:

Participants 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 participant s tumors. In some cases, a new biopsy may be needed.

Participants will receive up to 6 cycles of treatment.

The first cycle is 26 days: Participants 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 participants 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. Participants 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....

Clinical Trial Description

Background:

• Non-Hodgkin lymphoma (NHL) is the most common cancer among people living with 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 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 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 pomalidomide in combination with DA-EPOCH +/- Rituximab (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 antiretroviral therapy (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. ;

Related Conditions & MeSH terms

• B-Cell Neoplasm
• Burkitt Lymphoma
• Diffuse Large Cell Lymphoma
• Lymphoma
• Lymphoma, AIDS-Related
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Large-Cell, Immunoblastic
• Lymphoma, Non-Hodgkin
• Non-Hodgkin Lymphoma
• Plasmablastic Lymphoma

• NCT number: NCT05389423
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Anaida Widell
• Phone: (240) 760-6074
• Email: anaida.widell@nih.gov
• Status: Recruiting
• Phase: Phase 1
• Start date: June 27, 2023
• Completion date: June 1, 2032