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Daratumumab for Relapsed/Refractory Primary Effusion Lymphoma

Primary Purpose

Lymphoma, Primary Effusion

Status
Not yet recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Daratumumab SC
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma, Primary Effusion focused on measuring Kaposi Sarcoma Herpesvirus, HIV, CD38, B cell lymphoproliferative diseases, Non-Hodgkin Lymphoma

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • National Institutes of Health Clinical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm1

Arm Description

Treatment with daratumumab SC

Outcomes

Primary Outcome Measures

Overall response rate (ORR)
Percentage of participants with the best overall response of CR or PR to therapy

Secondary Outcome Measures

Safety of daratumumab
Adverse events (AEs) will be reported by type and grade of toxicity

Full Information

First Posted
June 15, 2023
Last Updated
October 24, 2023
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT05907759
Brief Title
Daratumumab for Relapsed/Refractory Primary Effusion Lymphoma
Official Title
A Phase II Study of Daratumumab for Relapsed/Refractory Primary Effusion Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
September 6, 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 30, 2023 (Anticipated)
Primary Completion Date
August 1, 2034 (Anticipated)
Study Completion Date
December 1, 2035 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, Primary Effusion
Keywords
Kaposi Sarcoma Herpesvirus, HIV, CD38, B cell lymphoproliferative diseases, Non-Hodgkin Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm1
Arm Type
Experimental
Arm Description
Treatment with daratumumab SC
Intervention Type
Drug
Intervention Name(s)
Daratumumab SC
Intervention Description
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 Information:
Title
Overall response rate (ORR)
Description
Percentage of participants with the best overall response of CR or PR to therapy
Time Frame
at 9 and 17 weeks, and every 12 weeks from week 25 to the end of therapy
Secondary Outcome Measure Information:
Title
Safety of daratumumab
Description
Adverse events (AEs) will be reported by type and grade of toxicity
Time Frame
From first dose through 30 days after the end of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Anaida Widell
Phone
(240) 760-6074
Email
anaida.widell@nih.gov
First Name & Middle Initial & Last Name or Official Title & Degree
Kathryn A Lurain, M.D.
Phone
(301) 250-5156
Email
kathryn.lurain@nih.gov
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kathryn A Lurain, M.D.
Organizational Affiliation
National Cancer Institute (NCI)
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Institutes of Health Clinical Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
National Cancer Institute Referral Office
Phone
888-624-1937

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
.All collected IPD will be shared
IPD Sharing Time Frame
Data from this study may be requested from other researchers at least 1 year after the completion of the primary endpoint.
IPD Sharing Access Criteria
Data from this study may be requested by contacting the PI.
Links:
URL
https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_001538-C.html
Description
NIH Clinical Center Detailed Web Page

Learn more about this trial

Daratumumab for Relapsed/Refractory Primary Effusion Lymphoma

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