Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, B-Cell

Lymphoma, AIDS-Related

Lymphoma, Primary Effusion

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

B-cell Lymphoma

Lymphosarcoma

Lymphoma AIDS Related

Primary Effusion Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Anti-Inflammatory Agents

Anti-Infective Agents

Etoposide

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Prednisone

Rituximab

Vincristine

Lenalidomide

Etoposide phosphate

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Tubulin Modulators

Antimitotic Agents

Angiogenesis Inhibitors

Growth Inhibitors

Lenalidomide, Rituximab, Prednisone, Etopiside, Doxorubicin, Vincristine and Cyclophosphamide

Lenalidomide taken orally, daily at assigned dose level on days 1 to 10, up to 25mg.

During cycle 1, rituximab will be administered on day 4 prior to the start of EPOCH. During cycles 2 to 6, rituximab will be administered on day 1 of each cycle.

During cycle 1, Prednisone 60 mg/m2 /day PO days 6 to 10. During cycles 2-6, Prednisone 60 mg/m2 /day PO days 1-5.

During cycle 1, Etoposide 50 mg/m2 /day continuous intravenous infusion days 6 to 9. During cycles 2-6, Etoposide 50 mg/m2/day continuous intravenous infusion days 1 to 4.

Etopside

During cycle 1, Doxorubicin 10 mg /m2/day continuous intravenous infusion days 6 to 9. During cycles 2-6, Doxorubicin continuous intravenous infusion days 1 to 4.

During cycle 1, Vincristine 0.4 mg/m2 /day continuous intravenous infusion days 6 to 9. During cycles 2-6, Vincristine continuous intravenous infusion days 1 to 4.

During cycle 1, Cyclophosphamide 750 mg/m2 day 10. During cycles 2-6, Cyclophosphamide 750 mg/m2 day 5.

Kathryn A Lurain, M.D.

Background:

Primary effusion lymphoma (PEL) is a rare disease with no standard treatment. Researchers want to see if a drug called lenalidomide along with common chemotherapy drugs may be effective in treating PEL.

Objective:

To test a new treatment for PEL.

Eligibility:

People ages 18 and older with PEL.

Design:

Participants will be screened with blood tests, imaging studies, a physical exam, and other tests.

Participants will have tests to evaluate their disease. These may include:

Blood tests

Scans

Lumbar puncture. Fluid around the spinal cord will be removed with a needle.

Bone marrow removed with a needle and studied

Samples of skin or lymph nodes removed

Fluid removed from around organs

Lung and eye tests

Tubes with cameras taking pictures of airways or digestive tract

Participants will take lenalidomide pills for 10 days. They will keep a pill diary.

Participants will have a catheter (small tube) placed in the large vein in the arm or chest.

Participants will get DA-EPOCH-R as intravenous infusions by catheter over several days. This will be repeated in 21-day cycles. Most participants will have 6 cycles.

Participants will get the drug filgrastim by injection under the skin. They will get the drug methotrexate injected into the spinal fluid.

During the study, participants will have the following tests done at least once:

Medical history

Physical exam

Blood, urine, and stool tests

Lesions photographed and measured

Lumbar puncture

Participants will have follow-up visits for 5 years. They will repeat the screening tests plus have urine and stool tested.

Participants may be contacted later by phone to see how they are doing.

Background

* Kaposi sarcoma herpesvirus (KSHV)-associated primary effusion lymphoma (PEL) is an aggressive B cell neoplasm with clinicopathologic and molecular profiles distinct from other AIDS-related lymphomas.
* There are no prospective studies on these rare lymphomas. Clinical experience is limited; however, reported prognosis is poor, with median survival estimated at less than 6 months using conventional CHOP-like chemotherapy.
* Novel treatment is urgently needed for KSHV-associated lymphomas, and the therapeutic approach must take into account concurrent KSHV-associated malignancies which are commonly seen in this patient population
* Lenalidomide, an immune-modulatory derivative of thalidomide (IMiD drug) has in vitro direct antitumor effect in KSHV-lymphomas as well as immune modulatory and anti-angiogenic effects that may be beneficial in treating PEL
* Rituximab, an anti-CD20 monoclonal antibody, has recently been shown to be an active agent in the management of KSHV-MCD. Although PEL is a CD20-negative tumor, advances in the understanding the biology of KSHV-infection of B-cells, the pathobiology of IL-6 syndromes in KSHV-MCD and KSHV-NHL, and clinical experience using rituximab in the treatment of KSHV-MCD, support use of rituximab in the treatment of PEL, especially in patients with concurrent KSHV-MCD.
* Modified dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA)-EPOCH is an anthracycline-based regimen that allows for personalization of dose-intensity showing that inclusion of etoposide and infusional administration decreases tumor cell resistance.
* The use of DA-EPOCH in combination with rituximab for the treatment of HIV associated diffuse large B-cell lymphoma or Burkitt lymphoma has been shown to be safe and effective.
* Given the central role of controlling HIV viremia with combination antiretroviral therapy (cART) in the management of KSHV-associated malignancies, as well as the likely contribution of uncontrolled HIV viremia to PEL pathogenesis, cART will be employed as an important part of the treatment regimen.

Objectives

Phase I

- Evaluate safety and tolerability of lenalidomide in combination with DA-EPOCH-R and determine the maximum tolerated dose and/or recommended phase II dose of this regimen.

Phase II

- Evaluate overall survival in treatment-na(SqrRoot) ve participants with KSHV-positive aggressive B cell lymphomas treated with lenalidomide in combination with DA-EPOCH and rituximab (DA-EPOCH-R\^2).

Eligibility

* Adult participants \>= 18 years with pathology confirmed any KSHV-positive aggressive B cell lymphomas, such as primary effusion lymphoma, and KSHV-associated large cell lymphoma
* Lymphoma that is measurable or assessable
* Any HIV status
* Hematologic and biochemical parameters within pre-specified limits at screening
* Willing to use effective birth control, as defined in the full protocol
* Neither pregnant nor breast feeding
* Excluded if other serious co-morbid condition that would prohibit administration of planned chemotherapeutic intervention is present

Design

* This is a phase I/ II study of lenalidomide in combination rituximab and modified DA-EPOCH (EPOCH-R\^2) in participants with KSHV-positive aggressive B cell lymphomas.
* Phase I of the study will evaluate lenalidomide 25 mg days 1-10 in combination with modified DA-EPOCH-R to determine safety and tolerability. Dose de-escalation doses of lenalidomide are 20 mg and 15 mg.
* Participants with HIV will generally be prescribed cART.
* In phase I, with up to 3 dose levels, 6-18 participants will be accrued (3-6 participants per level).
* In the phase II portion of the study, 15 evaluable participants will be enrolled over 48-60 months and 12 months follow-up after the last participant has enrolled, a 1-tailed 0.10 alpha level test would have 80% power to determine if OS curve would demonstrate a 1-year OS consistent with 45% or better and ruling out 20% or worse.

Lenalidomide Combined With Modified DA-EPOCH and Rituximab (EPOCH-R2) in Primary Effusion Lymphoma or KSHV-associated Large Cell Lymphoma

Phase I/II Study of Lenalidomide Combined With Modified DA-EPOCH and Rituximab (EPOCH-R2) in Primary Effusion Lymphoma or KSHV-Associated Large Cell Lymphoma

Association of treatment regimen with one-year overall survival

Median amount of time subject survives post therapy

Evaluate response rates and progression-free survival, and event-free survival for primary effusion lymphoma treated with DA-EPOCH-R2

Evaluate pharmacokinetics of lenalidomide in blood, effusion and CSF

In HIV infected patients, evaluate the effect of lenalidomide alone and in combination with EPOCH-R on HIV latency reversal and cellular measures of HIV

Evaluate the pharmacokinetics of tenofovir and tenofovir-diphosphate in plasma and PBMCs, respectively

National Cancer Institute (NCI)

Infections

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Symptoms and General Pathology

Acquired Immunodeficiency Syndrome

HIV Infections

Epstein-Barr Virus Infections

Lymphoma, Large B-Cell, Diffuse

Virus Diseases

Burkitt Lymphoma

Plasmablastic Lymphoma

Lymphoma, Large-Cell, Immunoblastic

Communicable Diseases

Herpesviridae Infections

DNA Virus Infections

Tumor Virus Infections

Diffuse Large B-Cell Lymphoma

Lymphoma, Large-cell, Immunoblastic

Pomalidomide

Pomalidomide (escalating doses) + Prednisone, Etoposide, Doxorubicin, Vincristin

Pomalidomide (at the MTD) + Prednisone, Etoposide, Doxorubicin, Vincristine and

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.

375 mg/m2 administered IV on day 1 (only for CD20+ tumors)

Anaida Widell

For more information at the NIH Clinical Center contact National Cancer Institute Referral Office

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....

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.

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

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

. All IPD recorded in the medical record will be shared with intramural investigators upon request.

The fraction of patients with toxicity noted at each dose level will be reported by grade and type of toxicity identified. Maximum tolerated dose will also be reported.

duration of time from the start of the treatment until time of disease relapse from PR, disease progression, or death, whichever occurs first

Percentage of participants with the best overall response of CR or PR to therapy

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Lenalidomide Combined With Modified DA-EPOCH and Rituximab (EPOCH-R2) in Primary Effusion Lymphoma or KSHV-associated Large Cell Lymphoma	NCT02911142	Primary Effusio... B-Cell Neoplasm	Lenalidomide Rituximab Prednisone Etopside Doxorubicin Vincristine Cyclophosphamid...	18 Years -	National Institutes of Health Clinical Center (CC)
Pomalidomide and Dose-Adjusted EPOCH +/- Rituximab for HIV-Associated Lymphomas	NCT05389423	Diffuse Large C... Non-Hodgkin Lym... Burkitt Lymphom... Plasmablastic L... B-Cell Neoplasm	Vincristine Prednisone Doxorubicin Etoposide Pomalidomide Cyclophosphamid... Rituximab	18 Years -	National Institutes of Health Clinical Center (CC)

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