Recruiting
Phase 2

Daratumumab

Sponsor:

National Cancer Institute (NCI)

Code:

NCT05907759

Conditions

Lymphoma, Primary Effusion

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Daratumumab SC

Study Details

Brief summary:

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.

Conditions

Lymphoma, Primary Effusion

Study ID

NCT05907759

Start date

Jul 10, 2024

Status verified date

Aug 21, 2026

Completion date

Dec 1, 2035

Anticipated

Primary completion date

Aug 1, 2034

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

  • 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.
  • No 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 Design

Enrollment

28 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm 1

Treatment with daratumumab SC

Interventions

Daratumumab SC

Daratumumab SC (daratumumab and hyaluronidase) is administered subcutaneously (SC) as 1800 mg/30,000 units weekly for a total of 8 weeks (8 doses) followed by every 2 weeks for a total of 16 weeks (8 doses) followed by every 4 weeks for up to 96 weeks (24 doses)

Primary outcome measure

  • Overall response rate (ORR) [ Time Frame: at 9 and 17 weeks, and every 12 weeks from week 25 to the end of therapy ]

Central Contacts and Locations

Central contacts

Anaida Widell

(240) 760-6074anaida.widell@nih.gov

Robert Yarchoan, M.D.

(240) 760-6075robert.yarchoan@nih.gov

Locations

National Institutes of Health Clinical Center

Recruiting

Bethesda, Maryland, United States, 20892

Contacts

National Cancer Institute Referral Office

888-624-1937

More Information

Sponsor

National Cancer Institute (NCI)

Last update posted

Aug 25, 2026

Last verified

Aug 21, 2026

Keywords

  • Multicentric Castleman Disease
  • Non-Hodgkin Lymphoma
  • Kaposi Sarcoma Herpesvirus
  • HIV
  • CD38
  • B cell lymphoproliferative diseases

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by National Cancer Institute (NCI) on 2026-08-25.