What side effects are associated with this type of intervention?

The most common treatments for Plasmablastic Lymphoma, such as Daratumumab combined with DA-EPOCH chemotherapy, have several known side effects. Daratumumab can lead to higher rates of infection, including pneumonia and severe lymphocytopenia, which may result in viral reactivations and fungal infections. The DA-EPOCH regimen, which includes etoposide, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride, often causes neutropenia, anemia, thrombocytopenia, peripheral neuropathy, and gastrointestinal symptoms like nausea and vomiting.

What prior FDA approvals exist?

Plasmablastic Lymphoma is a rare and aggressive form of non-Hodgkin lymphoma, and there are limited FDA-approved treatments specifically for this condition. However, daratumumab, a monoclonal antibody targeting CD38, has shown promise in treating cancers with high CD38 expression, such as multiple myeloma. While daratumumab is not specifically approved for Plasmablastic Lymphoma, its mechanism of targeting CD38-expressing cells is being studied in combination with standard chemotherapy regimens like DA-EPOCH (etoposide, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride) for potential effectiveness in treating this lymphoma.

What other types of research exist?

Promising, novel alternatives to Daratumumab for Plasmablastic Lymphoma patients in 2024 could include therapies targeting B-cell maturation antigen (BCMA) such as GSK2857916 (belantamab mafodotin) and CAR T-cell therapies like bb2121 (idecabtagene vicleucel). These therapies have shown efficacy in multiple myeloma, a related hematologic malignancy, and may offer potential benefits for Plasmablastic Lymphoma patients.

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Alkylating agents

Daratumumab + Chemotherapy for Lymphoma

Phase < 1

Waitlist Available

Led By Ariela Noy, MD

Research Sponsored by AIDS Malignancy Consortium

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Stage II-IV disease (Ann Arbor staging criteria) or stage I disease with elevated lactate dehydrogenase (LDH) or bulky tumor (> 7.5 cm).

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.

Must not have

Peripheral neuropathy grade ≥ 3 or neuropathic pain grade ≥ 2

Known or suspected parenchymal brain or spinal cord disease, or symptomatic leptomeningeal disease from lymphoma

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial studies how well daratumumab combined with chemotherapy works in treating patients with a specific type of lymphoma. The treatment targets cancer cells with a protein called CD38, helping the immune system attack them and stopping their growth. Daratumumab is a CD38 monoclonal antibody approved for treating relapsed/refractory and newly diagnosed multiple myeloma.

Who is the study for?

This trial is for adults with newly diagnosed stage I-IV plasmablastic lymphoma. Participants can be HIV-positive or negative but must meet specific criteria, including certain blood cell counts and organ function levels. They should not have had previous chemotherapy for lymphoma, except under certain conditions, and cannot have severe lung disease, active hepatitis B or C infections, brain metastases from solid tumors, or a history of allergic reactions to the study drugs.

What is being tested?

The trial tests daratumumab combined with DA-EPOCH chemotherapy (etoposide, prednisone, vincristine sulfate, cyclophosphamide, doxorubicin hydrochloride) in treating plasmablastic lymphoma. Daratumumab targets CD38 protein on cancer cells to help the immune system attack the cancer while chemotherapy aims to stop cancer growth by killing cells or preventing their division.

What are the potential side effects?

Potential side effects include infusion reactions related to daratumumab; nausea; hair loss; mouth sores; low blood cell counts leading to increased infection risk and bleeding problems; heart issues due to doxorubicin; nerve damage from vincristine causing numbness or pain.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My cancer is at an advanced stage or early stage with high LDH/bulky tumor.

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I have a tumor or cancer in my bone marrow that can be measured.

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My lymphoma has been confirmed through specific lab tests.

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My heart pumps well, with an ejection fraction of 45% or higher.

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I can take care of myself but might not be able to do active work.

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I can do most of my daily activities but might need help.

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I am HIV positive but haven't had any major HIV-related infections in the last year.

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My cancer is stage II-IV, or stage I with high LDH or a large tumor.

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My lymphoma has been confirmed through a biopsy.

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I am on HAART treatment for HIV, as prescribed by a doctor.

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My kidney function is within the normal range.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have severe nerve damage or pain.

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I do not have brain or spinal cord disease related to lymphoma.

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I have been diagnosed with Hepatitis C.

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I do not have any unmanaged ongoing illnesses.

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I had cancer before, but it's either cured or not related to my current condition.

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I have a serious, ongoing illness or infection that is not cancer.

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I am currently taking cobicistat, indinavir, ritonavir, or strong CYP3A4 inhibitors.

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I have COPD or asthma with severe breathing test results.

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I have brain metastases from a solid tumor.

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I have not had a heart attack in the last 6 months.

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I have been treated with daratumumab for another condition.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Cyclophosphamide

Secondary study objectives

Complete response (CR) rate

Incidence of adverse events

Overall survival (OS)

+1 more

Other study objectives

Changes in MYC expression

Changes in levels of Epstein Barr virus (EBV)

Circulating tumor DNA (ctDNA) in plasma

+1 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (daratumumab, DA-EPOCH)Experimental Treatment8 Interventions

Patients 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Doxorubicin

2012

Completed Phase 3

~8030

Doxorubicin Hydrochloride

2019

Completed Phase 3

~17860

Cyclophosphamide

2010

Completed Phase 4

~2310

Daratumumab

2014

Completed Phase 3

~2380

Etoposide

2010

Completed Phase 3

~2960

Prednisone

2014

Completed Phase 4

~2500

Vincristine

2003

Completed Phase 4

~2970

Vincristine Sulfate

2005

Completed Phase 3

~10270

0 / 22Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Plasmablastic Lymphoma (PBL) treatments often include a combination of chemotherapy and monoclonal antibodies. Chemotherapy agents like etoposide, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride work by killing cancer cells, stopping their division, or preventing their spread. Daratumumab, a monoclonal antibody targeting CD38, is particularly relevant for PBL because PBL cells express high levels of CD38. By binding to CD38, daratumumab helps the immune system attack and destroy these cancer cells, potentially enhancing the effectiveness of chemotherapy. This targeted approach is crucial for PBL patients as it may improve treatment outcomes by specifically targeting cancer cells while sparing normal cells.