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

NCT05907759 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 10001538001538-C
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)

  Percentage of participants with the best overall response of CR or PR to therapy

  at 9 and 17 weeks, and every 12 weeks from week 25 to the end of therapy

Secondary Outcomes (1)

• Safety of daratumumab

  From first dose through 30 days after the end of treatment

Study Arms (1)

Arm 1

EXPERIMENTAL

Treatment with daratumumab SC

Drug: Daratumumab SC

Interventions

Daratumumab SC DRUG

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)

Arm 1

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Lymphoma, Primary Effusion; Multi-centric Castleman's Disease; Lymphoma, Non-Hodgkin; Sarcoma, Kaposi

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms, Vascular Tissue

Study Officials

• Robert Yarchoan, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anaida Widell

CONTACT

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

Robert Yarchoan, M.D.

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2023
• First Posted: June 18, 2023
• Study Start: July 10, 2024
• Primary Completion (Estimated): August 1, 2034
• Study Completion (Estimated): December 1, 2035
• Last Updated: May 1, 2026

Record last verified: 2026-04-29

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data from this study may be requested from other researchers at least 1 year after the completion of the primary endpoint.
• Access Criteria: Data from this study may be requested by contacting the PI.

Locations

US (1)