A Study of Daratumumab and Dose-Adjusted EPOCH in Plasmablastic Lymphoma
A Multicenter, Open-Label Feasibility Study of Daratumumab With Dose-Adjusted EPOCH in Newly Diagnosed Plasmablastic Lymphoma With or Without HIV
3 other identifiers
interventional
15
1 country
8
Brief Summary
This feasibility trial studies how well daratumumab in combination with dose-adjusted etoposide, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride (DA-EPOCH) works in treating patients with newly diagnosed stage I-IV plasmablastic lymphoma. Plasmablastic lymphoma cells have high levels of a protein called CD38. Daratumumab is a monoclonal antibody that specifically targets CD38 expressing cells, and may help the body's immune system attack the cancer and interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as etoposide, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving daratumumab may enhance the effectiveness of a standard chemotherapy (DA-EPOCH) in patients with plasmablastic lymphoma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for early_phase_1
Started May 2021
Longer than P75 for early_phase_1
8 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 22, 2019
CompletedFirst Posted
Study publicly available on registry
October 25, 2019
CompletedStudy Start
First participant enrolled
May 24, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 1, 2030
June 29, 2025
June 1, 2025
8.1 years
October 22, 2019
June 26, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Percentage of newly diagnosed plasmablastic lymphoma patients who complete at least 3 cycles of daratumumab with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH)
The proportion of participants completing \>= 3 cycles of DA-EPOCH with daratumumab will be calculated with the denominator being eligible, evaluable participants.
Up to the completion of 3 cycles (each cycle is 21 days)
Secondary Outcomes (4)
Complete response (CR) rate
Up to the completion of 3 cycles (each cycle is 21 days)
Incidence of adverse events
Up to 2 years
Progression free survival (PFS)
Up to 1 year
Overall survival (OS)
Up to 1 year
Other Outcomes (4)
Changes in levels of Epstein Barr virus (EBV)
Baseline up to treatment completion, assessed up to 6 cycles (each cycle is 21 days)
Changes in MYC expression
Up to 2 years
EBV-associated tumor deoxyribonucleic acid (DNA) levels in plasma of participants with EBV positive (+) tumors
Up to 2 years
- +1 more other outcomes
Study Arms (1)
Treatment (daratumumab, DA-EPOCH)
EXPERIMENTALPatients receive daratumumab IV on days 1 (± 3 days), 8 (± 2 days), and 15 (± 2 days), of cycles 1-3, and on day 1 of cycles 4-6. Patients also receive etoposide, doxorubicin hydrochloride, and vincristine sulfate IV continuous over 96 hours on days 1-4, prednisone PO on days 1-5, and cyclophosphamide IV over 1 hour on day 5. Treatment repeats every 21 days for up to 6 cycles in absence of disease progression or unacceptable toxicity.
Interventions
Given IV
Given IV
Given IV
Given IV
Given IV
Given PO
Given IV
Given IV
Eligibility Criteria
You may qualify if:
- Participants must have histologically and immunophenotypically (via at least a core or ideally, incisional or excisional biopsy) documented plasmablastic lymphoma.
- Stage II-IV disease (Ann Arbor staging criteria) or stage I disease with elevated lactate dehydrogenase (LDH) or bulky tumor (\> 7.5 cm).
- Known HIV status. At most 7 HIV negative patients will be allowed on the study. Once 7 HIV negative patients have been enrolled, future enrollment will allow only HIV positive patients. Participants may be HIV positive, with documentation of HIV infection by means of any one of the following:
- Documentation of HIV diagnosis in the medical record by a licensed health care provider;
- Documentation of receipt of highly active antiretroviral therapy (HAART) (at least three different medications) by a licensed health care provider (documentation may be a record of an HAART prescription in the participant?s medical record, a written prescription in the name of the participant for HAART, or pill bottles for HAART with a label showing the participant?s name);
- HIV-1 ribonucleic acid (RNA) detection by a licensed HIV-1 RNA assay demonstrating \>1000 RNA copies/mL;
- Any licensed HIV screening antibody and/or HIV antibody/antigen combination assay confirmed by a second licensed HIV assay such as a HIV-1 Western blot confirmation or HIV rapid multispot antibody differentiation assay.
- NOTE: A ?licensed? assay refers to a U.S. Food and Drug Administration (FDA)-approved assay, which is required for all Investigational New Drug (IND) studies.
- Participants without HIV infection must have evidence of a negative result using any licensed HIV screening antibody assay and/or HIV antibody/antigen combination assay.
- Participants must have measurable disease (unless marrow-only disease is present), defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter) as \>= 15 mm (\>= 1.5cm) by computed tomography (CT) or positron emission tomography (PET) scan or evaluable by bone marrow.
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 50%).
- Absolute neutrophil count \>= 1,000 cells/mcL unless decreased due to bone marrow involvement.
- Platelets \>= 75,000 cells/mcL unless decreased due to bone marrow involvement.
- Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (\< 3.0 x ULN for patients with Gilbert syndrome). If, however, the elevated bilirubin is felt to be secondary to antiretroviral therapy, the total bilirubin must be =\< 3.5 mg/dL, provided that the direct bilirubin is normal and the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3 x the upper limit of normal.
- AST (serum glutamic oxaloacetic transaminase \[SGOT\])/ALT (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN (=\< 5 x ULN is acceptable if liver metastases are present).
- +7 more criteria
You may not qualify if:
- Prior cytotoxic chemotherapy or radiotherapy for this lymphoma other than palliative radiation for medical emergencies (like cord compression) or the following chemotherapy:
- A maximum of one cycle of combination chemotherapy, including EPOCH or CHOP-like therapy. The start of the previous chemotherapy cycle must occur at least 21 days but no more than 28 days prior to the beginning of therapy under this protocol, and such cycle will count towards the maximum of 6 cycles under this study (i.e., cycle off study will count as cycle 1 in terms of feasibility determination as per primary endpoint).
- One prior cycle of limited therapy including cyclophosphamide and/or glucocorticoids to improve performance status or hepatic or renal function impaired due to lymphoma involvement. The start of this therapy may occur up to 28 days prior to the beginning of study treatment under this protocol. Cyclophosphamide administration must have been completed at least 14 days prior to initiation of study treatment. Such treatment will not count towards the maximum of 6 cycles under this study (i.e., participants will receive 6 cycles on study).
- Patients who are receiving any other investigational agents.
- Participants must not have had previous anthracycline treatment within the last two years, except for liposomal doxorubicin. Any prior exposure to liposomal doxorubicin is allowed as long as the LVEF is ≥45%. It is at the discretion of the investigator if prior exposure to doxorubicin is acceptable.
- Participants who have previously received daratumumab for another indication.
- Participants must not be on cobicistat, indinavir, or ritonavir, or agents that are strong CYP3A4 inhibitors. If on a strong CYP3A4 inhibitor regimen prior to study enrollment, participants must be switched to alternative drugs at least one week prior to administration of study therapy.
- Participants with peripheral neuropathy grade ≥ 3 or neuropathic pain grade ≥ 2.
- Expected survival \< 2 months.
- Participants with known brain metastases from solid tumors will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- Patients with known or suspected parenchymal brain or spinal cord disease, and/or suspected or symptomatic leptomeningeal disease from lymphoma, prior to study enrolled will be excluded. Asymptomatic leptomeningeal disease only will be allowed.
- Patients who are seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]). All participants will be required to be screened for Hepatitis B. Participants with resolved infection (i.e., participants who are HBsAg negative but positive for antibodies to hepatitis B core antigen (anti-HBc) and/or antibodies to hepatitis B surface antigen (anti-HBs) must be screened using real-time polymerase chain reaction (PCR) measurement of HBV DNA levels. Participants who are PCR positive will be excluded. EXCEPTION: Participants with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR.
- Patients diagnosed with Hepatitis C who are Hepatitis C antibody positive, whether Hepatitis C RNA level is measurable or not, must have no evidence of cirrhosis and have liver function tests.
- History of allergic reactions, hypersensitivity, or intolerance attributed to compounds of similar chemical or biologic composition to daratumumab, or other agents used in the study or known sensitivity to mammalian-derived products.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- +10 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AIDS Malignancy Consortiumlead
- National Cancer Institute (NCI)collaborator
- Janssen Scientific Affairs, LLCcollaborator
- Montefiore Medical Centercollaborator
- Memorial Sloan Kettering Cancer Centercollaborator
- AIDS and Cancer Specimen Resourcecollaborator
- The Emmes Company, LLCcollaborator
Study Sites (8)
University of Miami Miller School of Medicine
Miami, Florida, 33136, United States
University of Illinois at Chicago
Chicago, Illinois, 60612, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21231, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10021, United States
University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, 27514, United States
The Ohio State University
Columbus, Ohio, 43210, United States
University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Ariela Noy, MD
Memorial Sloan Kettering Cancer Center
Study Design
- Study Type
- interventional
- Phase
- early phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NETWORK
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 22, 2019
First Posted
October 25, 2019
Study Start
May 24, 2021
Primary Completion (Estimated)
July 1, 2029
Study Completion (Estimated)
July 1, 2030
Last Updated
June 29, 2025
Record last verified: 2025-06