A Phase II Study of Daratumumab for Relapsed/Refractory Primary Effusion Lymphoma, Plasmablastic Lymphoma, and Multicentric Castleman Disease
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.
• Participants must have primary effusion lymphoma (PEL), including extracavitary variant and KSHV-associated large cell lymphoma, plasmablastic lymphoma (PBL), and/or KSHV-associated multicentric Castleman disease pathologically that relapsed and/or is refractory after front-line chemotherapy or be 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 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 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.