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

Descriptive Information
Brief Title † Lenalidomide Combined With Modified DA-EPOCH and Rituximab (EPOCH-R2) in Primary Effusion Lymphoma or KSHV-associated Large Cell Lymphoma
Official Title † Phase I/II Study of Lenalidomide Combined With Modified DA-EPOCH and Rituximab (EPOCH-R(2)) In Primary Effusion Lymphoma or KSHV-Associated Large Cell Lymphoma
Brief 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 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 antiangiogenic 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. Main 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 patients with primary effusion lymphoma treated with lenalidomide in combination with, DA-EPOCH and rituximab (DA-EPOCHR2). Eligibility - Adult patients greater than or equal to 18 years with pathology confirmed primary effusion lymphoma, including extracavitary variants, 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 DAEPOCH (EPOCH-R2) in patients with PEL and KSHV-associated large cell lymphoma - 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. - Patients with HIV will generally be prescribed cART. - In phase I, with up to 3 dose levels, 6-18 patients will be accrued (3-6 patients per level). - In the phase II portion of the study, 15 evaluable patients will be enrolled over 48-60 months and 12 months follow-up after the last patient 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.
Study Phase Phase 1/Phase 2
Study Type † Interventional
Study Design †
Primary Outcome Measure † (Phase I) Maximum tolerated dose of DA-EPOCH_R2
Secondary Outcome Measure †
Condition † Primary Effusion Lymphoma B-Cell Lymphoma
Intervention † DrugLenalidomide
Study Arms / Comparison Groups A Patients with PEL and KSHV-associated large cell lymphoma
Publications *

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information
Recruitment Status † Drug
Estimated Enrollment † 36
Start Date † September 15, 2016
Completion Date October 1, 2025
Primary Completion Date October 1, 2022
Eligibility Criteria † - INCLUSION CRITERIA: - Primary effusion lymphoma (PEL), including extracavitary variant, and KSHVassociated large cell lymphoma that is pathologically confirmed by the NCI Laboratory of Pathology - Measurable or assessable lymphoma. - Any HIV status - Age 18 years or greater. Because no dosing or adverse event data are currently available on the use of lenalidomide in combination with EPOCH-R in patients 1.5 times the upper limit of normal; AST and/or ALT > 3 times the upper limit of normal; EXCEPTIONS: - Total bilirubin greater than or equal to 5 mg/dL in patients with Gilbert's syndrome as defined by >80% unconjugated - Total bilirubin greater than or equal to 7.5 with direct fraction > 0.7 if patient is receiving a protease inhibitor at the time of initial evaluation - Hepatic dysfunction attributed to lymphoma, KSHV-MCD, or KICS - ANC
Gender All
Ages 18 Years - 99 Years
Accepts Healthy Volunteers No
Contacts †† Anaida Widell, (301) 451-3694,
Location Countries † United States
Administrative Information
NCT ID † NCT02911142
Organization ID 160171
Secondary IDs †† 16-C-0171
Responsible Party Sponsor
Study Sponsor † National Cancer Institute (NCI)
Collaborators ††
Investigators † Principal Investigator: Thomas S Uldrick, M.D., National Cancer Institute (NCI)
Information Provided By
Verification Date May 12, 2017
First Received Date † September 21, 2016
Last Updated Date May 31, 2017
† Required WHO trial registration data element.
†† WHO trial registration data element that is required only if it exists.
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