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

NCT02911142 | Active Not Recruiting Phase 1 Results FDA Drug

• 2 other identifiers: 16017116-C-0171
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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.

Conditions

Primary Effusion Lymphoma; B-Cell Neoplasm

Keywords

Treatment Naive; Immune Modulatory; Chemotherapy; AIDS-Related Lymphoma; PEL

Outcome Measures

Primary Outcomes (3)

• (Phase I) Maximum Tolerated Dose (MTD) of Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, and Rituximab (DA-EPOCH-R2)

  The MTD is the dose level at which no more than 1 of up to 6 participants experiences dose-limiting toxicity (DLT) during the first two cycles of DA-EPOCH-R2 treatment. Association of treatment regimen with one-year overall survival. DLT is defined as any grade 4 adverse event at least possibly related to lenalidomide and not probably or definitely related to human immunodeficiency virus (HIV) or a Kaposi sarcoma-associated herpesvirus KSHV-associated malignancy resulting in a dose delay in etoposide phosphate, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) treatment \>2 weeks due to failure to resolve to grade 3 or lower. Any grade 3 cardiac toxicity that is at least possibly related to lenalidomide and not probably or definitely related to HIV or a Kaposi sarcoma-associated herpesvirus (KSHV)-associated malignancy resulting in a dose delay in DA-EPOCH-R treatment \>2 weeks due to failure to resolve to grade 2 or lower.

  First 6 weeks of treatment (2 cycles of treatment)

• (Phase II) Overall Survival in Treatment-naive Participants With Primary Effusion Lymphoma Treated With Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, and Rituximab (DA-EPOCH-R2) Reported Along With a 90% Confidence Interval

  Median amount of time subject survives post therapy

  End of follow up period (5 years)

• (Phase II) Overall Survival in Treatment-naive Participants With Primary Effusion Lymphoma Treated With Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, and Rituximab (DA-EPOCH-R2) Reported Along With a 95% Confidence Interval

  Median amount of time subject survives post therapy.

  End of follow up period (5 years)

Secondary Outcomes (15)

• Response Rate for Primary Effusion Lymphoma Reported Using a 90% Confidence Interval

  Response rate was calculated at the end of treatment (18 weeks of treatment)

• Response Rate for Primary Effusion Lymphoma Reported Using a 95% Confidence Interval

  Response rate was calculated at the end of treatment (after 18 weeks of treatment)

• Progression-free Survival (PFS) for Primary Effusion Lymphoma Treated With Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, and Rituximab (DA-EPOCH-R2) Using a 90% Confidence Interval

  Over follow-up period, a median of 26 months

• Progression-free Survival (PFS) for Primary Effusion Lymphoma Treated With Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, and Rituximab (DA-EPOCH-R2) Using a 95% Confidence Interval

  Over a follow-up period, a median of 26 months

• Event-free Survival (EFS) for Primary Effusion Lymphoma Treated With Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, and Rituximab (DA-EPOCH-R2) Reported Along With a 90% Confidence Interval

  Over a follow-up period, a median of 26 months

Other Outcomes (2)

• Number of Participants With a Dose-limiting Toxicity (DLT)

  First 6 weeks (2 cycles) of treatment

• Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

  Median follow-up time was 26 months

Study Arms (1)

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

EXPERIMENTAL

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

Drug: Lenalidomide; Drug: Rituximab; Drug: Prednisone; Drug: Etoposide; Drug: Doxorubicin; Drug: Vincristine; Drug: Cyclophosphamide; Diagnostic Test: CT of neck, chest, abdomen and pelvis; Diagnostic Test: 18FDG-PET scan; Diagnostic Test: MRI Brain; Procedure: Bone marrow biopsy; Diagnostic Test: EKG; Diagnostic Test: Echocardiogram; Diagnostic Test: Ultrasound; Diagnostic Test: Bronchoscopy; Diagnostic Test: Endoscopy; Diagnostic Test: CXR: PA/lat/decub

Interventions

Lenalidomide DRUG

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

Also known as: Revlimid

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

Rituximab DRUG

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.

Also known as: Rituxan, Riabni, Ruxience, Truxima

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

Prednisone DRUG

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.

Also known as: Rayos, Deltasone, Prednisone Intensol

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

Etoposide DRUG

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.

Also known as: Toposar, Etopophos

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

Doxorubicin DRUG

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.

Also known as: Lipodox, Lipodox 50, Doxil

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

Vincristine DRUG

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.

Also known as: Oncovin, Marqibo, Vincasar PFS

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

Cyclophosphamide DRUG

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

Also known as: Cytoxan, Neosar, Endoxan

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

CT of neck, chest, abdomen and pelvis DIAGNOSTIC_TEST

Screening

Also known as: Computed tomography of neck, chest, abdomen and pelvis

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

18FDG-PET scan DIAGNOSTIC_TEST

Baseline

Also known as: 18 F-fluorodeoxyglucose-positron emission tomography scan

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

MRI Brain DIAGNOSTIC_TEST

Screening

Also known as: Magnetic resonance imaging brain

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

Bone marrow biopsy PROCEDURE

Baseline

Also known as: BM biopsy

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

EKG DIAGNOSTIC_TEST

Screening

Also known as: electrocardiogram

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

Echocardiogram DIAGNOSTIC_TEST

Screening

Also known as: ECHO

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

Ultrasound DIAGNOSTIC_TEST

Day 6

Also known as: U/S

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

Bronchoscopy DIAGNOSTIC_TEST

Baseline

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

Endoscopy DIAGNOSTIC_TEST

Baseline

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

CXR: PA/lat/decub DIAGNOSTIC_TEST

Screening

Also known as: Chest x-ray posteroanterior, lateral, decubitus

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Any Kaposi sarcoma herpesvirus (KSHV)-positive aggressive B cell lymphomas, such as primary effusion lymphoma (PEL), and KSHV-associated large cell lymphoma that is pathologically confirmed by the National Cancer Institute (NCI) Laboratory of Pathology
• Measurable or assessable lymphoma.
• Any human immunodeficiency virus (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 etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) in participants \<18 years of age, children are excluded from this study but may be eligible for future pediatric trials.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-4.
• Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 14 days prior to and again within 1 day before starting lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid Risk Evaluation and Mitigation Strategy (REMS) program. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy. All subjects must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control
• All study participants must agree to be registered into the mandatory REVLIMID REMS program, and be willing and able to comply with the requirements of the REVLIMID REMS program.
• Able to take aspirin 81mg orally daily or if intolerant of aspirin, able to take a substitute thromboprophylaxis such as low molecular weight heparin.
• Ability of subject to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Use of other systemic anticancer treatments or agents within the past 2 weeks. The use of rituximab for the treatment of KSHV-associated multicentric Castleman disease (MCD) or KSHV inflammatory cytokine syndrome (KICS) or the use of steroids are allowed within 2 weeks prior to start of treatment.
• Phase I or Phase II participants who have received prior dose-adjusted EPOCH for treatment for PEL or KSHV-associated large cell lymphoma
• Phase II participants who have received any prior curative-intent therapy for PEL or KSHV-associated large cell lymphoma. Participants who have received prior treatment as a bridge to curative-intent therapy will be considered per PI discretion.
• Parenchymal brain involvement with lymphoma
• History of malignant tumors other than KS or KSHV-associated MCD, unless:
• In complete remission for greater than or equal to 1 year from the time response was first documented or
• Completely resected basal cell carcinoma or
• In situ squamous cell carcinoma of the cervix or anus
• Inadequate renal function, defined as calculated or estimated creatinine clearance \< 60 mL/min unless lymphoma, KSHV-MCD, or KICS- related for calculation of creatinine clearance)
• Inadequate hepatic function
• Bilirubin (total) \> 1.5 times the upper limit of normal; aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \> 3 times the upper limit of normal; EXCEPTIONS:
• Total bilirubin greater than or equal to 5 mg/dL in participants with Gilbert's syndrome as defined by \>80% unconjugated
• Total bilirubin greater than or equal to 7.5 with direct fraction \> 0.7 if participants is receiving a protease inhibitor at the time of initial evaluation
• Hepatic dysfunction attributed to lymphoma, KSHV-MCD, or KICS
• Absolute neutrophil count (ANC) \<1000/mm\^3 and platelets \< 75,000/mm\^3 unless lymphoma, KSHV-MCD, or KICS- related.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Lymphoma, Primary Effusion; Lymphoma, B-Cell; Lymphoma, AIDS-Related

Interventions

Lenalidomide; Rituximab; Prednisone; Etoposide; etoposide phosphate; Doxorubicin; liposomal doxorubicin; Vincristine; Cyclophosphamide; Electrocardiography; Echocardiography; Ultrasonography; Bronchoscopy; Endoscopy

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Glucosides; Glycosides; Carbohydrates; Daunorubicin; Anthracyclines; Naphthacenes; Aminoglycosides; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Electrodiagnosis; Cardiac Imaging Techniques; Diagnostic Imaging; Diagnostic Techniques, Respiratory System; Diagnostic Techniques, Surgical; Minimally Invasive Surgical Procedures; Surgical Procedures, Operative; Pulmonary Surgical Procedures; Thoracic Surgical Procedures

Results Point of Contact

• Title: Dr. Ramya Ramaswami
• Organization: National Cancer Institute

ramya.ramaswami@nih.gov

240-506-1088

Study Officials

• Ramya Ramaswami, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 21, 2016
• First Posted: September 22, 2016
• Study Start: July 3, 2017
• Primary Completion: October 1, 2024
• Study Completion (Estimated): October 1, 2027
• Last Updated: July 28, 2025
• Results First Posted: July 28, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).

Locations

US (1)