Primary Effusion LymphomaPhase 1/2NCT02911142
Lenalidomide Combined With Modified DA-EPOCH and Rituximab (EPOCH-R2) in Primary Effusion Lymphoma or KSHV-associated Large Cell Lymphoma
A Phase 1/2 study testing Lenalidomide, Rituximab and Prednisone in people with Primary Effusion Lymphoma and B-Cell Neoplasm, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Effusion Lymphoma, B-Cell Neoplasm
- What is being tested?
- Lenalidomide, Rituximab and Prednisone
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Jul 2017to 1 Oct 2028
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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.
- Common Terminology Criteria for Adverse Events (CTCAE)v5.0 Grade 3-4 neuropathy
- Ejection fraction less than 40% by echocardiography
- Known drug-related, inherited, or acquired procoagulant disorder including prothrombin gene mutation 20210, antithrombin III deficiency, protein C deficiency, protein S deficiency and antiphospholipid syndrome but not including heterozygosity for the Factor V Leiden mutation or the presence of a lupus anticoagulant in the absence of other criteria for the antiphospholipid syndrome.
- History of hypersensitivity reactions attributed to thalidomide, lenalidomide, or pomalidomide, including prior development of erythema nodosum if characterized by a desquamating rash while taking thalidomide, lenalidomide, or pomalidomide.
- Breast feeding (if lactating, must agree not to breast feed while taking lenalidomide). Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with lenalidomide, breastfeeding should be discontinued if the mother is treated with lenalidomide.
- Uncontrolled severe intercurrent illness including, but not limited to bacterial, fungal, or life-threatening viral infection; symptomatic congestive heart failure; unstable angina pectoris; cardiac arrhythmia; or psychiatric illness/social situations that would limit compliance with study requirements. Participants with severe intercurrent illnesses attributed to lymphoma, KSHV-MCD, or KICS may be eligible per principal investigators (PI's) or designees' discretion.
- Any condition, including laboratory abnormalities, which in the opinion of the Principal Investigator or Lead Associate Investigator, would prohibit administration of planned chemotherapeutic intervention, places the subject at unacceptable risk if they were to participate in the study or confounds the ability to interpret data from the study
- Pregnant women are excluded from this study because lenalidomide is a Category X agent with the potential for teratogenic or abortifacient effects. These potential risks may also apply to other agents used in this study.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: 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
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.
Read more
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.
Read the 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
- Being tested
- Lenalidomide, Rituximab, Prednisone, Etoposide, Doxorubicin
- Keywords
- Treatment Naive, Immune Modulatory, Chemotherapy, AIDS-Related Lymphoma, PEL
- Medical subject headings
- Lymphoma, Primary Effusion, Lymphoma, B-Cell, Lymphoma, AIDS-Related
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LenalidomideDrug
Also called Revlimid
Lenalidomide taken orally, daily at assigned dose level on days 1 to 10, up to 25mg.
RituximabDrug
Also called Rituxan, Riabni, Ruxience, Truxima
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.
PrednisoneDrug
Also called Rayos, Deltasone, Prednisone Intensol
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.
EtoposideDrug
Also called Toposar, Etopophos
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.
DoxorubicinDrug
Also called Lipodox, Lipodox 50, Doxil
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.
VincristineDrug
Also called Oncovin, Marqibo, Vincasar PFS
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.
CyclophosphamideDrug
Also called Cytoxan, Neosar, Endoxan
During cycle 1, Cyclophosphamide 750 mg/m^2 day 10. During cycles 2-6, Cyclophosphamide 750 mg/m^2 day 5.
CT of neck, chest, abdomen and pelvisDiagnostic test
Also called Computed tomography of neck, chest, abdomen and pelvis
Screening
18FDG-PET scanDiagnostic test
Also called 18 F-fluorodeoxyglucose-positron emission tomography scan
Baseline
MRI BrainDiagnostic test
Also called Magnetic resonance imaging brain
Screening
Bone marrow biopsyProcedure or surgery
Also called BM biopsy
Baseline
EKGDiagnostic test
Also called electrocardiogram
Screening
EchocardiogramDiagnostic test
Also called ECHO
Screening
UltrasoundDiagnostic test
Also called U/S
Day 6
BronchoscopyDiagnostic test
Baseline
EndoscopyDiagnostic test
Baseline
CXR: PA/lat/decubDiagnostic test
Also called Chest x-ray posteroanterior, lateral, decubitus
Screening
| Study group | Role | What they receive |
|---|---|---|
| Lenalidomide, Rituximab, Prednisone, Etoposide, Doxorubicin, Vincristine and Cyclophosphamide | Experimental | Lenalidomide, Rituximab, Prednisone, Etoposide, Doxorubicin, Vincristine and Cyclophosphamide Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
(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.
Measured: 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
Measured: 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.
Measured: End of follow up period (5 years)
Secondary outcomes (15)
Response Rate for Primary Effusion Lymphoma Reported Using a 90% Confidence Interval
Response rate is defined as the percentage of participants who have either a complete response (CR) or partial response (PR) for primary effusion lymphoma treated with etoposide phosphate, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R2) measured by the International Working Group Response Criteria for Malignant Lymphomas. Complete response (CR) is complete disappearance of all detectable evidence of disease. Partial response (PR) is at least a ≥50% decrease in the sum of the product of the diameters of up to 6 of the largest dominant nodes or nodal masses.
Measured: 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 is defined as the percentage of participants who have either a Complete Response (CR) or Partial Response (PR) for primary effusion lymphoma treated with etoposide phosphate, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R2) measured by the International Working Group Response Criteria for Malignant Lymphomas. Complete response (CR) is complete disappearance of all detectable evidence of disease. Partial response (PR) is at least a ≥50% decrease in the sum of the product of the diameters of up to 6 of the largest dominant nodes or nodal masses.
Measured: 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
PFS is defined as the duration of time from start of treatment to time of progression of Kaposi sarcoma-associated herpesvirus (KSHV)-lymphoma or death, whichever occurs first, measured by the International Working Group Response Criteria for Malignant Lymphoma. Progressive disease is appearance of any new nodal lesion ≥1.6 cm in greatest transverse diameter (GTD) or ≥1.1 cm in short axis during or after the end of therapy, even if other lesions are decreasing in size. At least a 50% increase from the nadir in the sum of the product of the diameters (SPD) of any previously involved nodes, or in a single involved node, or in the size of other lesions (e.g., splenic or hepatic nodules).
Measured: 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
PFS is defined as the duration of time from start of treatment to time of progression of Kaposi sarcoma-associated herpesvirus (KSHV)-lymphoma or death, whichever occurs first, measured by the International Working Group Response Criteria for Malignant Lymphoma. Progressive disease is appearance of any new nodal lesion ≥1.6 cm in greatest transverse diameter (GTD) or ≥1.1 cm in short axis during or after the end of therapy, even if other lesions are decreasing in size. At least a 50% increase from the nadir in the sum of the product of the diameters (SPD) of any previously involved nodes, or in a single involved node, or in the size of other lesions (e.g., splenic or hepatic nodules).
Measured: 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
Event-Free Survival (EFS) is defined as the duration of time from start of treatment to time of progression of Kaposi sarcoma-associated herpesvirus (KSHV)-lymphoma. Progressive disease was measured by the International Working Group Response Criteria for Malignant Lymphoma. Progressive disease is the appearance of any new nodal lesion ≥1.6 cm in greatest transverse diameter (GTD) or ≥1.1 cm in short axis during or after the end of therapy, even if other lesions are decreasing in size. At least a 50% increase from the nadir in the sum of the product of the diameters (SPD) of any previously involved nodes, or in a single involved node, or in the size of other lesions (e.g., splenic or hepatic nodules).
Measured: 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 95% Confidence Interval
Event-Free Survival (EFS) is defined as the duration of time from start of treatment to time of progression of Kaposi sarcoma-associated herpesvirus (KSHV)-lymphoma. Progressive disease was measured by the International Working Group Response Criteria for Malignant Lymphoma. Progressive disease is the appearance of any new nodal lesion ≥1.6 cm in greatest transverse diameter (GTD) or ≥1.1 cm in short axis during or after the end of therapy, even if other lesions are decreasing in size. At least a 50% increase from the nadir in the sum of the product of the diameters (SPD) of any previously involved nodes, or in a single involved node, or in the size of other lesions (e.g., splenic or hepatic nodules).
Measured: Over a follow-up period, a median of 26 months
Response Assessment of Kaposi Sarcoma Using the Modified Acquired Immunodeficiency Syndrome (AIDS) Clinical Trials Criteria Reported Along With a 90% Confidence Interval
Response was assessed by the percentage of participants with either a partial or complete response. Response was assessed using the Modified Acquired Immunodeficiency Syndrome (AIDS) Clinical Trials Criteria. Complete Response is the absence of any detectable residual disease, including tumor associated edema, persisting for at least 4 weeks. The absence of any detectable residual disease, including tumor associated edema, persisting for at least 4 weeks. Partial Response is a 50% or greater decrease in the number and/or size of previously existing lesions lasting for at least 4 weeks or no new lesions occurring in previously uninvolved areas of the body.
Measured: At end of treatment (after 18 weeks treatment)
Response Assessment of Kaposi Sarcoma Using the Modified Acquired Immunodeficiency Syndrome (AIDS) Clinical Trials Criteria Reported Along With a 95% Confidence Interval
Response was assessed by the percentage of participants with either a partial or complete response. Response was assessed using the Modified Acquired Immunodeficiency Syndrome (AIDS) Clinical Trials Criteria. Complete Response is the absence of any detectable residual disease, including tumor associated edema, persisting for at least 4 weeks. The absence of any detectable residual disease, including tumor associated edema, persisting for at least 4 weeks. Partial Response is a 50% or greater decrease in the number and/or size of previously existing lesions lasting for at least 4 weeks or no new lesions occurring in previously uninvolved areas of the body.
Measured: At end of treatment (after 18 weeks of treatment)
Response Rate of Participants With Active Multicentric Castleman Disease (MCD) Assessed by the National Cancer Institute (NCI) MCD Response Criteria Reported Along With a 90% Confidence Interval
Response rate is calculated by the percentage of participants with either a partial or complete response. Complete Response (CR) is full resolution of all clinical symptoms and laboratory abnormalities (whether or not these are indicator abnormalities) probably or definitely attributable to MCD, lasting at least 3 weeks. Partial Response (PR) is at least 50% of the abnormalities probably or definitely attributed to Kaposi sarcoma-associated herpesvirus (KSHV)-MCD must improve by the minimum amounts specified to attain PR (e.g., C-reactive protein reduction to ≤50% of baseline; and Hemoglobin increment 2g/dL not explained by transfusion).
Measured: At end of treatment (after 18 weeks of treatment)
Response Rate of Participants With Active Multicentric Castleman Disease (MCD) Assessed by the National Cancer Institute (NCI) MCD Response Criteria Reported Along With a 95% Confidence Interval
Response rate is calculated by the percentage of participants with either a partial or complete response. Complete Response (CR) is full resolution of all clinical symptoms and laboratory abnormalities (whether or not these are indicator abnormalities) probably or definitely attributable to MCD, lasting at least 3 weeks. Partial Response (PR) is at least 50% of the abnormalities probably or definitely attributed to Kaposi sarcoma-associated herpesvirus (KSHV)-MCD must improve by the minimum amounts specified to attain PR (e.g., C-reactive protein reduction to ≤50% of baseline; and Hemoglobin increment 2g/dL not explained by transfusion).
Measured: At end of treatment (after 18 weeks of treatment)
Kaposi's Sarcoma-associated Herpesvirus (KSHV)-Associated Inflammatory Cytokine Syndrome (KICS) Reported Along With a 90% Confidence Interval
Complete Response (CR) is full resolution of all clinical symptoms and laboratory abnormalities (whether or not these are indicator abnormalities) probably or definitely attributable to KICS, lasting at least 3 weeks. Partial Response (PR) is at least 50% of the abnormalities probably or definitely attributed to KICS must improve by the minimum amounts (e.g., C-reactive protein reduction to ≤50% of baseline; and Hemoglobin increment 2g/dL not explained by transfusion). Progressive disease (PD) is at least two indicator abnormalities must deteriorate by the minimum amounts specified below to constitute PD (e.g., C-reactive protein increase by ≥50% of baseline (or the upper limit of normal, whichever is greater); Hemoglobin decrement 2g/dL not otherwise explained; and Platelet decrement ≥25,000/mm^3 not otherwise explained). Stable disease (SD) is no change in signs and symptoms of KICS that meet criteria for any of CR, PR or PD.
Measured: At the end of treatment (after 18 weeks of treatment)
Kaposi's Sarcoma-associated Herpesvirus (KSHV)-Associated Inflammatory Cytokine Syndrome (KICS) Reported Along With a 95% Confidence Interval
Complete Response (CR) is full resolution of all clinical symptoms and laboratory abnormalities (whether or not these are indicator abnormalities) probably or definitely attributable to KICS, lasting at least 3 weeks. Partial Response (PR) is at least 50% of the abnormalities probably or definitely attributed to KICS must improve by the minimum amounts (e.g., C-reactive protein reduction to ≤50% of baseline; and Hemoglobin increment 2g/dL not explained by transfusion). Progressive disease (PD) is at least two indicator abnormalities must deteriorate by the minimum amounts specified below to constitute PD (e.g., C-reactive protein increase by ≥50% of baseline (or the upper limit of normal, whichever is greater); Hemoglobin decrement 2g/dL not otherwise explained; and Platelet decrement ≥25,000/mm^3 not otherwise explained). Stable disease (SD) is no change in signs and symptoms of KICS that meet criteria for any of CR, PR or PD.
Measured: At the end of treatment (after 18 weeks of treatment)
Pharmacokinetics of Lenalidomide in Blood
Bioanalytical measurements will be conducted on an ultra-high-performance liquid chromatography (uHPLC) with tandem mass spectrometric detection to determine the concentration of lenalidomide in blood using an assay developed and validated by the National Institutes of Health (NIH) Clinical Pharmacology Program.
Measured: Cycle 1 Day 1(C1D1), C1D7, C6D1 (one cycle = 21 days)
Pharmacokinetics of Lenalidomide Effusion
Bioanalytical measurements will be conducted on an ultra-high-performance liquid chromatography (uHPLC) with tandem mass spectrometric detection to determine the concentration of lenalidomide in effusions using an assay developed and validated by the National Institutes of Health (NIH) Clinical Pharmacology Program.
Measured: Cycle 1 Day 1(C1D1), C1D7, C6D1 (one cycle = 21 days)
Pharmacokinetics of Lenalidomide in Cerebrospinal Fluid (CSF)
Bioanalytical measurements will be conducted on an ultra-high-performance liquid chromatography (uHPLC) with tandem mass spectrometric detection to determine the concentration of lenalidomide in CSF using an assay developed and validated by the National Institutes of Health (NIH) Clinical Pharmacology Program.
Measured: Cycle 1 Day 1(C1D1), C1D7, C6D1 (one cycle = 21 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2016 (estimated)
- Study start3 Jul 2017
- Primary completion1 Oct 2024
- Study completion1 Oct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Primary Effusion LymphomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Ramya Ramaswami, National Cancer Institute (NCI)
- Investigators
- Ramya Ramaswami, MBBS, MPH, Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02911142
- Sponsor's protocol ID
- 160171
- Other IDs
- 16-C-0171
- Status last verified
- Sep 2026
- First submitted
- 21 Sep 2016
- Last updated
- 20 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.