Daratumumab for Relapsed/Refractory Primary Effusion Lymphoma

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Not yet recruiting

CT.gov ID

NCT05907759

Collaborator

(none)

Enrollment

Location

Arm

149.1

Anticipated Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Background:

Primary effusion lymphoma (PEL) is an aggressive form of cancer that affects cells in the immune system and lymph nodes. How PEL develops is not well understood, and this disease does not respond well to standard treatments for other types of lymphomas.

Objective:

To test a drug treatment (daratumumab SC) in people with PEL.

Eligibility:

People aged 18 and older with PEL. Their PEL 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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, Primary Effusion	Drug: Daratumumab SC	Phase 2

Detailed Description

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.
Immunophenotypically, PEL is a post-germinal center B cell neoplasm expressing surface markers consistent with plasmacytic differentiation, such as CD45, CD38, CD138, MUM-1, and IRF4, similar to that of multiple myeloma.
Outcomes for PEL 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.
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 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 who are ineligible for front-line chemotherapy

Eligibility

Age >=18 years
Pathologically confirmed relapsed and/or refractory primary effusion lymphoma (PEL), including extracavitary variant and KSHV-associated large cell lymphoma or ineligible for front line chemotherapy
Participants with PEL must have:
Measurable or assessable disease
ECOG Performance Status (PS) 0-3
Received first-line curative-intent therapy for PEL, unless such therapy is contraindicated

Design

This is a Phase 2 study to evaluate the response rate of daratumumab SC in participants with relapsed/refractory PEL
The study will accrue up to 12 evaluable participants with PEL
Daratumumab SC will be administered subcutaneously (SC) as 1800 mg/30,000 units weekly for a total of 8 doses followed by every 2 weeks for a total of 8 doses followed by every 4 weeks for up to 24 months in the absence of off-treatment criteria.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

16 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Study of Daratumumab for Relapsed/Refractory Primary Effusion Lymphoma

Anticipated Study Start Date :

Jun 29, 2023

Anticipated Primary Completion Date :

Aug 1, 2034

Anticipated Study Completion Date :

Dec 1, 2035

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm1 Treatment with daratumumab SC	Drug: 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)

Arm

Intervention/Treatment

Experimental: Arm1

Treatment with daratumumab SC

Drug: 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)

Outcome Measures

Primary Outcome Measures

Overall response rate (ORR) [at 9 and 17 weeks, and every 12 weeks from week 25 to the end of therapy]
Percentage of participants with the best overall response of CR or PR to therapy

Secondary Outcome Measures

Safety of daratumumab [From first dose through 30 days after the end of treatment]
Adverse events (AEs) will be reported by type and grade of toxicity

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

INCLUSION CRITERIA:
Participants must have primary effusion lymphoma (PEL), including extracavitary variant and KSHV-associated large cell lymphoma that relapsed and/or is refractory after front-line chemotherapy or be ineligible for front-line chemotherapy. Note: Participants must have pathologic confirmation of the disease diagnosis (at any time) confirmed by NCI Laboratory of Pathology.
Age >= 18 years.
Any HIV status
Those with HIV must have CD4 count >= 100 cells/(micro)L or CD4 >= 50 cells/(micro)L if CD4 was >= 100 cells/(micro)L prior to front-line chemotherapy
Participants with HIV must be receiving or willing to initiate an effective combination antiretroviral therapy (ART) regimen
Participants with PEL must meet the following criteria:
Must have measurable or assessable lymphoma
ECOG performance status 0-3
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-containing chemotherapy) for PEL, 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).
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 setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy.
People of child-bearing potential and those who can father children must agree to use dual form of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and for 3 months after the last dose.
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.
Participants may not receive investigational agents on other clinical trials.
Kaposi sarcoma requiring urgent treatment with cytotoxic chemotherapy.
Bilirubin (total) > 1.5 times the upper limit of normal; AST and/or ALT > 3 times the upper limit of normal; 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/mm3 and platelets < 75,000/mm3 unless related to lymphoma or prior therapy.
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 III-IV).
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-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.