Pomalidomide and Dose-Adjusted EPOCH +/- Rituximab for HIV-Associated Lymphomas
- Conditions
- Diffuse Large Cell LymphomaNon-Hodgkin LymphomaBurkitt LymphomaPlasmablastic LymphomaB-Cell Neoplasm
- Interventions
- Registration Number
- NCT05389423
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 25
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description 1/Dose Escalation Vincristine Pomalidomide (escalating doses) + Prednisone, Etoposide, Doxorubicin, Vincristin 1/Dose Escalation Prednisone Pomalidomide (escalating doses) + Prednisone, Etoposide, Doxorubicin, Vincristin 1/Dose Escalation Doxorubicin Pomalidomide (escalating doses) + Prednisone, Etoposide, Doxorubicin, Vincristin 1/Dose Escalation Etoposide Pomalidomide (escalating doses) + Prednisone, Etoposide, Doxorubicin, Vincristin 1/Dose Escalation Pomalidomide Pomalidomide (escalating doses) + Prednisone, Etoposide, Doxorubicin, Vincristin 1/Dose Escalation Cyclophosphamide Pomalidomide (escalating doses) + Prednisone, Etoposide, Doxorubicin, Vincristin 2/Dose Expansion Vincristine Pomalidomide (at the MTD) + Prednisone, Etoposide, Doxorubicin, Vincristine and 1/Dose Escalation Rituximab Pomalidomide (escalating doses) + Prednisone, Etoposide, Doxorubicin, Vincristin 2/Dose Expansion Etoposide Pomalidomide (at the MTD) + Prednisone, Etoposide, Doxorubicin, Vincristine and 2/Dose Expansion Prednisone Pomalidomide (at the MTD) + Prednisone, Etoposide, Doxorubicin, Vincristine and 2/Dose Expansion Doxorubicin Pomalidomide (at the MTD) + Prednisone, Etoposide, Doxorubicin, Vincristine and 2/Dose Expansion Cyclophosphamide Pomalidomide (at the MTD) + Prednisone, Etoposide, Doxorubicin, Vincristine and 2/Dose Expansion Pomalidomide Pomalidomide (at the MTD) + Prednisone, Etoposide, Doxorubicin, Vincristine and 2/Dose Expansion Rituximab Pomalidomide (at the MTD) + Prednisone, Etoposide, Doxorubicin, Vincristine and
- Primary Outcome Measures
Name Time Method safety and tolerability 6 cycles of treatment, or until confirmed progression, unacceptable toxicity or trial withdrawal 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.
- Secondary Outcome Measures
Name Time Method progression-free survival 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). duration of time from the start of the treatment until time of disease relapse from PR, disease progression, or death, whichever occurs first
preliminary estimates of response 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). Percentage of individuals with the best overall response of CR or PR to therapy
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States