NCT02911142

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

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 17 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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 cyclophosphamide, doxorubicin, vincristine, prednisone (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-cluster of differentiation 20 (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-Multicentric Castleman disease (MCD) and KSHV-non-Hodgkin lymphoma (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 human immunodeficiency virus (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-naive 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 overall survival (OS) curve would demonstrate a 1-year OS consistent with 45% or better and ruling out 20% or worse.

Conditions

• Primary Effusion Lymphoma
• B-Cell Neoplasm

Interventions

Type	Name	Description
DRUG	Lenalidomide	Lenalidomide taken orally, daily at assigned dose level on days 1 to 10, up to 25mg.
DRUG	Rituximab	During cycle 1, rituximab will be administered on day 4 prior to the start of etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH). During cycles 2 to 6, rituximab will be administered on day 1 of each cycle.
DRUG	Prednisone	During cycle 1, Prednisone 60 mg/m\^2 /day by mouth (PO) days 6 to 10. During cycles 2-6, Prednisone 60 mg/m\^2 /day PO days 1-5.
DRUG	Etoposide	During cycle 1, Etoposide 50 mg/m\^2 /day continuous intravenous infusion days 6 to 9. During cycles 2-6, Etoposide 50 mg/m\^2/day continuous intravenous infusion days 1 to 4.
DRUG	Doxorubicin	During cycle 1, Doxorubicin 10 mg /m\^2/day continuous intravenous infusion days 6 to 9. During cycles 2-6, Doxorubicin continuous intravenous infusion days 1 to 4.
DRUG	Vincristine	During cycle 1, Vincristine 0.4 mg/m\^2 /day continuous intravenous infusion days 6 to 9. During cycles 2-6, Vincristine continuous intravenous infusion days 1 to 4.
DRUG	Cyclophosphamide	During cycle 1, Cyclophosphamide 750 mg/m\^2 day 10. During cycles 2-6, Cyclophosphamide 750 mg/m\^2 day 5.
DIAGNOSTIC_TEST	CT of neck, chest, abdomen and pelvis	Screening
DIAGNOSTIC_TEST	18FDG-PET scan	Baseline
DIAGNOSTIC_TEST	MRI Brain	Screening
PROCEDURE	Bone marrow biopsy	Baseline
DIAGNOSTIC_TEST	EKG	Screening
DIAGNOSTIC_TEST	Echocardiogram	Screening
DIAGNOSTIC_TEST	Ultrasound	Day 6
DIAGNOSTIC_TEST	Bronchoscopy	Baseline
DIAGNOSTIC_TEST	Endoscopy	Baseline
DIAGNOSTIC_TEST	CXR: PA/lat/decub	Screening

Timeline

• Start date: 2017-07-03
• Primary completion: 2024-10-01
• Completion: 2027-10-01
• First posted: 2016-09-22
• Last updated: 2025-07-28
• Results posted: 2025-07-28

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study