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.
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).
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);
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.
Single group
Cyclophosphamide
DrugGiven IV
Daratumumab
Biological/VaccineGiven IV
Doxorubicin
DrugGiven IV
Doxorubicin Hydrochloride
DrugGiven IV
Etoposide
DrugGiven IV
Prednisone
DrugGiven PO
Vincristine
DrugGiven IV
Vincristine Sulfate
DrugGiven IV
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.
Complete response (CR) rate
Defined by the 2017 Response Evaluation Criteria in Lymphoma (RECIL) Criteria.
Incidence of adverse events
The frequency of various adverse events and proportion of participants affected will be calculated. Toxicity data will be presented by type and severity. Incidence of toxicity related dose reductions and treatment discontinuations will be summarized.
Progression free survival (PFS)
Will be estimated by Kaplan-Meier method as well as the corresponding 95% confidence intervals.
Overall survival (OS)
Will be estimated by Kaplan-Meier method as well as the corresponding 95% confidence intervals.
Changes in levels of Epstein Barr virus (EBV)
Descriptive statistics will be used to evaluate the changes in levels of EBV copy number from baseline (before initiation of treatment), compared with levels after cycles 1 and 2 and at treatment completion.
Changes in MYC expression
Descriptive statistics will be used to assess the effect of daratumumab and DA-EPOCH on MYC expression by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) and IHC panels of the microenvironment.
EBV-associated tumor deoxyribonucleic acid (DNA) levels in plasma of participants with EBV positive (+) tumors
Descriptive statistics will be used to evaluate the effect of daratumumab and DA-EPOCH on EBV-associated tumor DNA levels in the plasma of participants with EBV+ tumors.
Circulating tumor DNA (ctDNA) in plasma
Descriptive statistics will be used to evaluate the effect of daratumumab and DA-EPOCH on ctDNA in the plasma of all participants.
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AIDS Malignancy Consortium
Lead sponsor
National Cancer Institute (NCI)
Collaborator
Janssen Scientific Affairs, LLC
Collaborator
Montefiore Medical Center
Collaborator
Memorial Sloan Kettering Cancer Center
Collaborator
AIDS and Cancer Specimen Resource
Collaborator
The Emmes Company, LLC
Collaborator
