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A Study of Daratumumab and Dose-Adjusted EPOCH in Plasmablastic Lymphoma | Clinical Trials | Clareo Health

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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

NCT04139304•AIDS Malignancy Consortium

View on ClinicalTrials.gov

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.

Detailed Description

PRIMARY OBJECTIVES: 1\. To evaluate the feasibility of adding daratumumab to DA-EPOCH by assessing the percentage of PBL patients who complete ≥3 cycles of study treatment per protocol. SECONDARY OBJECTIVES: 1. To estimate the complete response (CR) rate as defined by the 2017 RECIL Criteria in HIV positive and HIV negative patients with plasmablastic lymphoma treated with daratumumab and DA-EPOCH. 2. To evaluate the safety of dose-adjusted EPOCH with daratumumab as assessed by the NCI CTCAE version 5.0. 3. To estimate the overall survival (OS), progression free survival (PFS), and event free survival (EFS) at 1 year. EXPLORATORY OBJECTIVES: 1. To explore the relationship of tumor characteristics as determined by immunohistochemistry (IHC) panels and fluorescent in situ hybridization (FISH) and clinical outcomes. 2. To assess the relationship between EBV-tumor association and EBV plasma copy number and to assess any prognostic significance of clearance of viral DNA from plasma during or at the end of therapy 3. To determine the feasibility of identifying circulating tumor DNA (ctDNA) as reflected in plasma DNA mutation panels or clonal immunoglobulin DNA and to and to assess any prognostic significance of clearance of tumor DNA from plasma during therapy. OUTLINE: Patients receive daratumumab intravenously (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 orally (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 the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for up to 2 years.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•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.
+12 more criteria

Exclusion Criteria

•1. 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).
•OR
•• 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).
•2. Patients who are receiving any other investigational agents.
•3. 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.
•4. Participants who have previously received daratumumab for another indication.
•5. 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.
•6. Participants with peripheral neuropathy grade ≥ 3 or neuropathic pain grade ≥ 2.
•7. Expected survival \< 2 months.
+17 more criteria

Locations (8)

University of Miami Miller School of Medicine

Miami, Florida, United States

University of Illinois at Chicago

Chicago, Illinois, United States

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, United States

The Ohio State University

Columbus, Ohio, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Key Dates

Start Date

May 24, 2021

Primary Completion Date

July 1, 2029

Completion Date

July 1, 2030

Last Updated

June 29, 2025

Enrollment

ESTIMATED participants

Conditions

Plasmablastic LymphomaAnn Arbor Stage I Diffuse Large B-Cell LymphomaAnn Arbor Stage II Diffuse Large B-Cell LymphomaAnn Arbor Stage III Diffuse Large B-Cell LymphomaAnn Arbor Stage IV Diffuse Large B-Cell Lymphoma

Interventions

Cyclophosphamide

DRUG

Daratumumab

BIOLOGICAL

Doxorubicin

DRUG

Doxorubicin Hydrochloride

DRUG

Etoposide

DRUG

Prednisone

DRUG

Vincristine

DRUG

Vincristine Sulfate

DRUG

Gene Therapy in Treating Patients With Human Immunodeficiency Virus-Related Lymphoma Receiving Stem Cell Transplant

NCT02797470

HIV InfectionMature T-Cell and NK-Cell Non-Hodgkin Lymphoma+9 more

View study

Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: June 29, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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