A Study of Daratumumab and Dose-Adjusted EPOCH in Plasmablastic Lymphoma
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|ClinicalTrials.gov Identifier: NCT04139304|
Recruitment Status : Recruiting
First Posted : October 25, 2019
Last Update Posted : November 3, 2021
|Condition or disease||Intervention/treatment||Phase|
|Plasmablastic Lymphoma Ann Arbor Stage I Diffuse Large B-Cell Lymphoma Ann Arbor Stage II Diffuse Large B-Cell Lymphoma Ann Arbor Stage III Diffuse Large B-Cell Lymphoma Ann Arbor Stage IV Diffuse Large B-Cell Lymphoma||Drug: Cyclophosphamide Biological: Daratumumab Drug: Doxorubicin Drug: Doxorubicin Hydrochloride Drug: Etoposide Drug: Prednisone Drug: Vincristine Drug: Vincristine Sulfate||Early Phase 1|
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.
- 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.
- To evaluate the safety of dose-adjusted EPOCH with daratumumab as assessed by the NCI CTCAE version 5.0.
- To estimate the overall survival (OS), progression free survival (PFS), and event free survival (EFS) at 1 year.
- To explore the relationship of tumor characteristics as determined by immunohistochemistry (IHC) panels and fluorescent in situ hybridization (FISH) and clinical outcomes.
- 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
- 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.
Patients receive daratumumab intravenously (IV) on days 1, 8, and 15 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Multicenter, Open-Label Feasibility Study of Daratumumab With Dose-Adjusted EPOCH in Newly Diagnosed Plasmablastic Lymphoma|
|Actual Study Start Date :||May 24, 2021|
|Estimated Primary Completion Date :||August 2022|
|Estimated Study Completion Date :||August 2024|
Experimental: Treatment (daratumumab, DA-EPOCH)
Patients receive daratumumab IV on days 1, 8, and 15 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.
Drug: Doxorubicin Hydrochloride
Drug: Vincristine Sulfate
- 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) [ Time Frame: Up to the completion of 3 cycles (each cycle is 21 days) ]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 [ Time Frame: Up to the completion of 3 cycles (each cycle is 21 days) ]Defined by the 2017 Response Evaluation Criteria in Lymphoma (RECIL) Criteria.
- Incidence of adverse events [ Time Frame: Up to 2 years ]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) [ Time Frame: Up to 1 year ]Will be estimated by Kaplan-Meier method as well as the corresponding 95% confidence intervals.
- Overall survival (OS) [ Time Frame: Up to 1 year ]Will be estimated by Kaplan-Meier method as well as the corresponding 95% confidence intervals.
- Changes in levels of Epstein Barr virus (EBV) [ Time Frame: Baseline up to treatment completion, assessed up to 6 cycles (each cycle is 21 days) ]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 [ Time Frame: Up to 2 years ]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 [ Time Frame: Up to 2 years ]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 [ Time Frame: Up to 2 years ]Descriptive statistics will be used to evaluate the effect of daratumumab and DA-EPOCH on ctDNA in the plasma of all participants.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04139304
|United States, Maryland|
|Johns Hopkins University/Sidney Kimmel Cancer Center||Recruiting|
|Baltimore, Maryland, United States, 21231|
|Contact: Laura Clark, PA-C 410-502-5396 email@example.com|
|Principal Investigator: Richard Ambinder, MD|
|United States, New York|
|Memorial Sloan Kettering Cancer Center||Recruiting|
|New York, New York, United States, 10021|
|Contact: Ariela Noy, MD 212-639-7423 firstname.lastname@example.org|
|Principal Investigator: Ariela Noy, MD|
|United States, North Carolina|
|University of North Carolina - Chapel Hill||Recruiting|
|Chapel Hill, North Carolina, United States, 27514|
|Contact: Christopher Dittus, DO, MPH 984-974-0000 email@example.com|
|Principal Investigator: Christopher Dittus, DO, MPH|
|United States, Ohio|
|The Ohio State University||Recruiting|
|Columbus, Ohio, United States, 43210|
|Contact: Lisa Brenner 614-293-7843 Lisa.Brenner@osumc.edu|
|Principal Investigator: Robert Baiocchi, MD, PhD|
|Principal Investigator:||Ariela Noy, MD||Memorial Sloan Kettering Cancer Center|