Daratumumab for Relapsed/Refractory Primary Effusion Lymphoma

• INCLUSION CRITERIA:

• Participants must have primary effusion lymphoma (PEL), including extracavitaryvariant and KSHV-associated large cell lymphoma and/or KSHV-associated multicentricCastleman disease pathologically that relapsed and/or is refractory after front-linechemotherapy or be ineligible for front-line chemotherapy. Note: Participants musthave pathologic confirmation of the disease diagnosis (at any time) confirmed by NCILaboratory of Pathology.

• Age >= 18 years.

• Any HIV status

• Those with HIV must have CD4 count >= 100 cells/microL or CD4 >= 50 cells/microL ifCD4 was >= 100 cells/microL prior to front-line chemotherapy

• Participants with HIV must be receiving or willing to initiate an effectivecombination antiretroviral therapy (ART) regimen

• Participants with PEL must meet the following criteria:

• Must have measurable or assessable lymphoma

• ECOG performance status 0-2 or 3 if secondary to PEL

• Adequate hematological and renal functions as defined below:

• Hemoglobin (Hgb) > 7 g/dL

• Creatinine clearance (CrCl) >= 30 mL/min/1.73 m^2

• Must have received first-line curative-intent therapy (anthracycline-containingchemotherapy) for PEL, unless such therapy is contraindicated due to infectionthat precludes combination chemotherapy (such as progressive multifocalleukoencephalopathy) or if there is a contraindication to receiving CHOP orEPOCH (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) >= 30 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 viral load.

• Participants who are seropositive for hepatitis C are eligible only in the settingof a sustained virologic response [SVR], defined as aviremia at least 12 weeks aftercompletion of antiviral therapy.

• Participants that have received investigational agents on other clinical trials musthave had a washout period of 2 weeks or 5 drug half-lives, whichever is longer.

• Women of child-bearing potential (WOBP) must agree to use an effective (dual) formof contraception (barrier, surgical sterilization, abstinence) prior to study entryand for the duration of study participation and for 3 months after the last dose ofstudy drug.

• Men must agree to use an effective method of contraception (barrier, surgicalsterilization, abstinence) for the duration of the study treatment and up to 3months after the last dose of the study drug(s). We also will recommend men withfemale partners of childbearing potential to ask female partners to be on aneffective birth control (hormonal, intrauterine device (IUD), surgicalsterilization).

• Breastfeeding participants must be willing to discontinue breastfeeding from studytreatment 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 thecancer treatment is for a malignancy whose natural history or treatment does nothave the potential to interfere with the safety or efficacy assessment of theinvestigational regimen are eligible for this trial, such as local treatment forcarcinoma in situ or hormonal therapy for prostate or breast carcinoma. Toxicityrelated to prior therapies other than hair loss and neuropathy must have resolved tograde 1.

• Kaposi sarcoma requiring urgent treatment with cytotoxic chemotherapy.

• Bilirubin (total) > 1.5 times the upper limit of normal; AST and/or ALT > 3 timesthe upper limit of normal; EXCEPTIONS:

• Total bilirubin >= 5 mg/dL in participants with Gilbert's syndrome as definedby > 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/orKSHV-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 oruncontrolled disease/condition related to or affecting cardiac function (e.g.,unstable angina, congestive heart failure, New York Heart Association ClassIIIIV).

• Uncontrolled cardiac arrhythmia

• Chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1second (FEV1) < 50% of predicted normal.

• Moderate or severe persistent asthma within the past 2 years, or uncontrolled asthmaof any classification. Note that participants who currently have controlledintermittent asthma or controlled mild persistent asthma are allowed to participatein the study.

• Pregnant people as evaluated by a positive serum or urine Beta-hCG test

• Participants with severe uncontrolled intercurrent illness, evaluated by history,physical exam and chemistry panel. Participants with severe intercurrent illnessesattributed to lymphoma may be eligible per PI s or designee s discretion.