ClinicalTrials.gov record NCT05907759

Daratumumab for Relapsed/Refractory Primary Effusion Lymphoma, Plasmablastic Lymphoma, and Multicentric Castleman Disease

Record copied from ClinicalTrials.gov: Oct 10, 2026AI summaries generated: Sep 28, 2026

A Phase II Study of Daratumumab for Relapsed/Refractory Primary Effusion Lymphoma, Plasmablastic Lymphoma, and Multicentric Castleman Disease

StatusRecruitingThe study is currently enrolling participants. Only the study team can say whether a particular person can join.
Study typeInterventionalA study in which researchers assign participants to one or more interventions, such as a drug, procedure, device, behavioural programme or other approach, to measure their effects.
PhasePhase 2A study that tests whether a treatment has the intended effect and continues to check safety, usually in a larger group than phase 1.
Age18 years old to 120 years old
SexAll
LocationUnited States
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

This Phase 2 study gives daratumumab as a subcutaneous injection to people with relapsed/refractory primary effusion lymphoma (PEL), plasmablastic lymphoma (PBL), or symptomatic KSHV‑associated multicentric Castleman disease (MCD). Treatment follows a weekly, then every-2-weeks, then every-4-weeks schedule for up to the durations described in the registry. Participants will have screening and monitoring tests including scans, blood tests, and possible procedures such as lumbar puncture or thoracentesis, and will be followed during treatment and for up to 5 years.

What it is studying. Whether subcutaneous daratumumab produces complete or partial responses in people with relapsed/refractory PEL, PBL, or symptomatic KSHV‑MCD, measured mainly by overall response rate (complete + partial responses) at scheduled time points.

What the researchers hope to learn. To measure the overall response rate (partial plus complete responses) to subcutaneous daratumumab in relapsed/refractory PEL and PBL and in symptomatic KSHV‑MCD, and to collect safety data on adverse events.

What this study is about

The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.

Background: Primary effusion lymphoma (PEL), plasmablastic lymphoma (PBL), and Multicentric Castleman Disease (MCD) are aggressive forms of cancer that affects cells in the immune system and lymph nodes. How they develop is not well understood, and these diseases do not respond well to standard treatments for other types of lymphomas. Objective: To test a drug treatment (daratumumab SC) in people with PEL, PBL, or MCD. Eligibility: People aged 18 and older with PEL, PBL, or MCD who must have failed to respond to therapy or they must be unable to receive standard treatment for the disease. Design: Participants will be screened. They will have a physical exam with blood tests. They will have imaging scans and tests of their heart and lung function. They may need to have a biopsy: tissue or fluid will be collected. They will have an eye exam. Daratumumab SC is given as an injection into the fat under the skin in the abdomen. This takes 3 to 5 minutes. Participants will receive the treatment once a week for 8 weeks; then every 2 weeks for 16 weeks; then every 4 weeks for up to 24 months. Participants will have other tests during the study period. These may include lumbar punctures: A needle will be inserted between the bones of the spine to draw some fluid from the area around the spinal cord. Participants may also have a thoracentesis: A needle or plastic tube will be inserted into the space around the lungs to withdraw fluid. Participants will have more imaging scans and blood tests. Follow-up visits will continue after treatment ends. Participants will be in the study for up to 5 years.

Interventions being studied

Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.

Drug
  • Daratumumab SC

Eligibility

The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.

Inclusion criteria

  • Participants with histologically confirmed primary effusion lymphoma (PEL) including extracavitary and KSHV-associated large cell lymphoma variants, plasmablastic lymphoma (PBL), and/or KSHV-associated multicentric Castleman disease (MCD) that has relapsed, and/or is refractory after frontline chemotherapy, or who are ineligible for front-line chemotherapy
  • Age >= 18 years.
  • Any HIV status
  • Participants with HIV must be receiving or will initiate an effective combination antiretroviral therapy (ART) regimen and must have an undetectable HIV VL which is defined as <200 copies/mL.
  • Participants with PEL or PBL must meet the following criteria:
  • Must have measurable or assessable lymphoma
  • ECOG performance status (PS) 0-2 or 3 if secondary to PEL or PBL
  • Adequate hematological and renal functions as defined below:
  • Hemoglobin (Hgb) > 7 g/dL
  • Creatinine clearance (CrCl) >= 15 mL/min/1.73 m\^2
  • Must have received first-line curative-intent therapy (anthracycline-containing chemotherapy) for PEL or PBL, unless such therapy is contraindicated due to infection that precludes combination chemotherapy (such as progressive multifocal leukoencephalopathy) or if there is a contraindication to receiving CHOP or EPOCH (such as multi-organ failure).
  • Participants with KSHV-MCD must meet the following criteria:
  • ECOG performance status (PS) 0-2 or 3 if secondary to MCD
  • Adequate hematological and renal functions as defined below:
  • Hemoglobin (Hgb) > 7 g/dL
  • Creatinine clearance (CrCl) >= 15 mL/min/1.73 m\^2
  • At least one clinical symptom attributed to KSHV-MCD
  • Fever (>38 degrees Celsius)
  • Fatigue
  • Gastrointestinal symptoms
  • Respiratory/sinus symptoms
  • Rash
  • At least one laboratory abnormality attributed to KSHV-MCD
  • Anemia (Hgb [men] < 12.5 g/dL, Hgb [women] < 11 g/dL)
  • Thrombocytopenia (< 150 K/microL)
  • Hypoalbuminemia (< 3.4 g/dL)
  • Hyponatremia (< 135 mmol/L)
  • Elevated C-reactive protein (CRP) (> 3 mg/L)
  • For participants with evidence of chronic hepatitis B virus (HBV) infection, participants must be on suppressive therapy with an undetectable VL.
  • Participants who are seropositive for hepatitis C virus (HCV)are eligible only in the setting of a sustained virologic response [SVR], defined as aviremia, at least 12 weeks after completion of antiviral therapy.
  • Participants that have received investigational agents on other clinical trials must have had a washout period of 2 weeks or 5 drug half-lives, whichever is longer.
  • Women of child-bearing potential (WOCBP) must agree to use an effective (dual) form of contraception (barrier, surgical sterilization, abstinence) prior to study entry and for the duration of study participation and for 3 months after the last dose of study drug. WOCBP must refrain from egg donations during the study and for 3 months after the last dose of daratumumab.
  • Men must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) for the duration of the study treatment and up to 3 months after the last dose of the study drug(s). We also will recommend men with female partners of childbearing potential to ask female partners to be on an effective birth control (hormonal, intrauterine device [IUD], surgical sterilization).
  • Breastfeeding participants must be willing to discontinue breastfeeding from study treatment initiation through 3 months after the last dose of the study drug.
  • Participants must understand and sign a written informed consent document.

Exclusion criteria

  • Participants who have had anticancer treatment within the last 2 weeks unless the cancer treatment is for a malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial, such as local treatment for carcinoma in situ or hormonal therapy for prostate or breast carcinoma. Toxicity related to prior therapies other than hair loss and neuropathy must have resolved to grade 1.
  • KS requiring urgent treatment with cytotoxic chemotherapy.
  • 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 (ULN);
  • EXCEPTIONS:
  • Total bilirubin >= 5 mg/dL in participants with Gilbert's syndrome as defined by > 80% unconjugated
  • If the elevated total bilirubin or AST/ALT are due to ART or lymphoma
  • ANC < 1000/mm\^3 and platelets < 75,000/mm\^3 unless related to lymphoma and/or KSHV-MCD or prior therapy.
  • Life-threatening or organ-threatening manifestations of KSHV-MCD.
  • Clinically significant cardiac disease, including:
  • Myocardial infarction within 6 months of randomization, or an unstable or uncontrolled disease/condition related to or affecting cardiac function (e.g., unstable angina, congestive heart failure, New York Heart Association Class IIIIV).
  • Uncontrolled cardiac arrhythmia
  • Chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) < 50% of predicted normal.
  • Moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification. Note that participants who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to participate in the study.
  • Pregnant people as evaluated by a positive serum or urine beta-human chorionic gonadotropin (Beta-hCG) test
  • Participants with severe uncontrolled intercurrent illness, evaluated by history, physical exam and chemistry panel. Participants with severe intercurrent illnesses attributed to lymphoma may be eligible per PI s or designee s discretion.

Study description and what participation involves

The study's detailed description, as published on ClinicalTrials.gov.

Show the detailed description from the registry

Background

  • Primary effusion lymphoma (PEL) is an aggressive B-cell lymphoma caused by the Kaposi sarcoma herpesvirus (KSHV) with clinicopathologic and molecular profiles distinct from other HIV-related lymphomas.
  • Plasmablastic lymphoma (PBL) is an aggressive B-cell lymphoma frequently caused by Epstein-Barr virus (EBV) with frequent extranodal presentations involving the bones and gastrointestinal tract.
  • Immunophenotypically, PEL and PBL are post-germinal center B cell neoplasms expressing surface markers consistent with plasmacytic differentiation, such as CD45, CD38, CD138, MUM-1, and IRF4, similar to that of multiple myeloma (MM).
  • Outcomes for PEL and PBL treated with front-line combination chemotherapy are inferior to those of other HIV-associated lymphomas, and second-line cytotoxic chemotherapy is often ineffective, and profound immunosuppression often prevents this approach.
  • In the second-line setting, chemotherapy-sparing treatments that do not contribute to further immune suppression may be more effective. In addition, patients with PEL often have concurrent KS, which can be severely exacerbated by immune suppression and contributes to mortality in PEL.
  • Kaposi sarcoma herpesvirus-associated multicentric Castleman disease (KSHV-MCD) is a rare lymphoproliferative disorder that develops predominantly in people with HIV with inflammatory symptoms associated with high levels of interleukin-6 (IL-6), KSHV-encoded viral IL-6 (vIL-6), and other cytokines.
  • The pathologic hallmark of KSHV-MCD is the presence of KSHV-infected Lambda-restricted plasmablasts in the mantle zones of lymph nodes which stain brightly for CD45 and CD38 and negative for CD20.
  • KSHV-MCD is generally treated with the anti-CD20 monoclonal antibody, rituximab, with the goal to rapidly improve symptoms and eliminate reservoirs of KSHV-infected plasmablasts.
  • Concurrent Kaposi sarcoma is often exacerbated by or develops during rituximab therapy and contributes to morbidity in KSHV-MCD.
  • Daratumumab is a human monoclonal antibody that binds to a unique region on CD38 and induces killing of CD38-expressing cells via antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and apoptosis.
  • Daratumumab also depletes immunosuppressive non-plasma cells that express CD38 thereby reducing local immunosuppression and stimulating an increase in T-helper cells, cytotoxic T cells, T-cell functional response, and T-cell receptor (TCR) clonality in the tumor microenvironment.

Objective -To evaluate the partial response (PR) plus complete response (CR) rate (further referred to as the overall response rate [ORR]) of daratumumab SC in participants with relapsed/refractory PEL or PBL and/or symptomatic KSHV-MCD or who are ineligible for front-line chemotherapy Eligibility

  • Age >=18 years
  • Participants with pathologically confirmed relapsed and/or refractory PEL, including extracavitary variant and KSHV-associated large cell lymphoma, PBL, or ineligible for front line chemotherapy
  • Participants with PEL or PBL must have:
  • Measurable or assessable disease
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-3
  • Received first-line curative-intent therapy for PEL or PBL, unless such therapy is contraindicated
  • Participants with KSHV-MCD must have:
  • ECOG PS 0-2 or 3 if secondary to PEL or PBL/MCD
  • At least one clinical symptom and at least one laboratory abnormality attributable to KSHV-MCD

Design

  • This is a Phase 2 study to evaluate the response rate of daratumumab SC in participants with relapsed/refractory PEL or PBL, and/or symptomatic KSHV-MCD.
  • The study will accrue up to 12 evaluable participants with PEL or PBL and up to 12 evaluable participants with KSHV-MCD.
  • For participants with relapsed/refractory PEL or PBL, daratumumab SC will be administered subcutaneously (SC) as 1800 mg/30,000 units weekly for a total of 8 weeks followed by every 2 weeks for a total of 16 weeks followed by every 4 weeks for up to 96 weeks in the absence of off-treatment criteria. Participants who are deriving benefit from therapy and exhibit disease worsening without meeting the criteria for progression may resume therapy every two weeks for up to 96 weeks.
  • Participants with relapsed/refractory PEL or PBL who are benefiting from treatment but show progression in effusions or CSF may continue therapy for up to an additional 3 months.
  • For participants with symptomatic KSHV-MCD, daratumumab SC will be administered SC as 1800 mg/30,000 units weekly for 8 weeks. If response assessment indicates progressive or stable disease, daratumumab SC will be given every 2 weeks for up to 24 weeks (6 months).
AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

Participants will have screening tests such as a physical exam, blood tests, imaging scans, heart and lung function tests, and an eye exam; a tissue or fluid biopsy may be collected at screening. Treatment is daratumumab given as a subcutaneous injection into the abdominal fat (about 3–5 minutes) — weekly for 8 weeks, then every 2 weeks for 16 weeks, then every 4 weeks for up to 96 weeks. During the study you may also have lumbar punctures (spinal fluid collection) and thoracentesis (fluid removed from around the lungs), plus additional imaging and blood tests. Follow-up visits continue after treatment ends and total participation may last up to 5 years.

How the study is structured. Interventional Phase 2, single-group, non‑masked study: all participants receive daratumumab given under the skin (subcutaneous). Participants are screened, receive the study drug on the schedule in the registry (weekly for 8 weeks, then every 2 weeks, then every 4 weeks with durations that differ by condition), and undergo periodic scans and laboratory tests. Response is assessed at specified weeks (including at weeks 9 and 17, then every 12 weeks from week 25). Safety is monitored through reported adverse events.

Questions you could ask

These questions are suggestions for a conversation with the study team or your own clinician, not advice.

  • The registry lists this study under Lymphoma, Primary Effusion. Does it apply to my diagnosis?
  • The listed sites are in United States. Is any of them reachable for me, and does the study help with travel?
  • Which of the eligibility criteria would need to be checked with tests before I could join?

More on Castleman disease

Clinical trials14 trials listed for Castleman diseaseEvery trial the registry lists for Castleman disease, with recruitment status, phase and sites, updated from ClinicalTrials.gov.See all trials →Research updatesWhat changed in Castleman disease researchLatest monthly update: September 2026. Includes: Unicentric tumor removal. New research summarized each month in plain language, with links to every source paper.Read the latest update →

Important dates

Study start
Jul 10, 2024
Primary completion
Aug 1, 2034 (estimated)
Study completion
Dec 1, 2035 (estimated)
Target enrollment
40 participants (estimated)
Last updated on registry
Sep 25, 2026
Data verified
Oct 10, 2026

Sponsor and research team

The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.

Lead sponsor
National Cancer Institute (NCI)

Central study contact

If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.

Participating sites (1)

  • National Institutes of Health Clinical CenterRecruiting

    Bethesda, Maryland, 20892 · United States

Terms used on this page · explanations by MedicalUpdates.ai

standard treatment
Treatment generally considered appropriate for a condition in a particular clinical setting. It can vary by patient, place and over time. In many studies the new treatment is added to, or compared with, standard of care.
biopsy
Removal of a small piece of tissue so it can be examined under a microscope. 'Biopsy-proven' or 'histologically confirmed' means the diagnosis was confirmed by examining tissue under a microscope.
Follow-up
The period after treatment or enrolment during which participants are observed or contacted, for example to record side effects or outcomes.
relapsed
A condition that improved with treatment and has since returned or worsened.
refractory
A condition that has not responded to a treatment. 'Relapsed' means it responded and then came back; 'refractory' means it did not respond in the first place.
ECOG performance status
A scale from 0 to 5 that describes how a person's condition affects daily activity. 0 means fully active; 1 means restricted in strenuous activity; 2 means able to self-care but unable to work; higher numbers mean more limitation.
Creatinine clearance
A measure of kidney function, calculated from a blood creatinine level together with age, weight and sex.
contraindicated
A reason a particular test or treatment should not be used for a person, for example a metal implant that rules out an MRI scan.
investigational
A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
washout period
A period during which a participant stops a previous treatment before starting the study treatment, so the earlier treatment does not affect the results.
half-lives
The time it takes for the amount of a drug in the body to fall by half. 'Five half-lives' is often used as the point at which a previous drug has essentially left the body.
WOCBP
Studies often ask participants who could become pregnant, or could father a child, to use contraception during the study and for a period afterwards, because the effect of the treatment on a pregnancy is unknown.
written informed consent
The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
natural history
A study that follows how a condition changes over time without assigning an experimental treatment. It may involve study visits and tests, and is often used to plan future trials.
upper limit of normal
The highest value of a blood test that a laboratory considers normal. Criteria such as '≤ 3 × ULN' mean the result must be no more than three times that value.
ANC
The number of neutrophils, a type of white blood cell that fights infection, in a blood sample. Studies often require it to be above a set level.
prior therapy
Treatment a person has already had for the condition. A 'line of therapy' is one course of treatment; studies often require, or limit, the number of prior lines.
randomization
Participants are assigned to the study groups by chance, like a coin toss, rather than chosen by the doctor or the participant. This is done so the groups are comparable.
INCLUSION CRITERIA
The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
EXCLUSION CRITERIA
The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
immunosuppressive
A medicine that reduces the activity of the immune system. Studies of autoimmune conditions often require a stable dose, a prior failure, or a washout of such medicines.
complete response
No sign of the condition can be found with the tests used in the study. It does not always mean the condition is gone permanently, and the definition depends on the condition and the study.

The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.

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