This phase II trial evaluates whether loncastuximab tesirine and rituximab followed by dose-adjusted doxorubicin, etoposide, vincristine, cyclophosphamide, and prednisone works to treat patients with high risk diffuse large B-cell lymphoma. Loncastuximab tesirine is a monoclonal antibody called loncastuximab, linked to a drug called tesirine. It is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as CD19 receptors, and delivers tesirine to kill them. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Chemotherapy drugs such as doxorubicin, vincristine, and cyclophosphamide 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. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill cancer cells. Prednisone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Giving loncastuximab tesirine and rituximab in combination with dose-adjusted doxorubicin, etoposide, vincristine, cyclophosphamide, and prednisone may be more effective at treating high risk diffuse large B-cell lymphoma patients than standard treatments.
Histologically or cytologically confirmed untreated DEL and DHL diffuse large B-cell lymphoma (DLBCL) meeting the World Health Organization (WHO) criteria for DEL - MYC greater than 40% and BCL2 greater than 50% by immunohistochemistry, or high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (double-hit and/or triple-hit are included)
Measurable disease by CT or PET/CT scan, with one or more sites of disease >= 1.5 cm in longest dimension
Age >= 18 years at time of consent
Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
1 cycle of DA-EPOCH-R or rituximab, cyclophosphamide, doxorubicin (Adriamycin) vincristine (Oncovin) and prednisolone (R-CHOP)
Radiotherapy > 2 weeks of initiating study treatment
Nitrosoureas or mitomycin C > 6 weeks of initiating study treatment
Steroid treatment for DLBCL or steroid monotherapy to stabilize disease while awaiting fluorescence in situ hybridization (FISH)
Single group
Cyclophosphamide
DrugGiven IV
Doxorubicin
DrugGiven IV
Etoposide
DrugGiven IV
Loncastuximab Tesirine
Biological/VaccineGiven IV
Prednisone
DrugGiven PO
Rituximab
Biological/VaccineGiven IV
Vincristine
DrugGiven IV
Complete response rate
Evaluated per 2014 Lugano criteria. An exact 95% confidence interval will be calculated.
Overall survival rate
Will be estimated using the product-limit of Kaplan and Meier.
Relapse/progression free survival
Will be estimated using the product-limit of Kaplan and Meier.
Overall response rate (complete response + partial response)
Defined as the proportion of participants who have partial or complete response from the start of study treatment through completion of 2 cycles. Evaluated per 2014 Lugano criteria. An exact 95% confidence interval will be calculated.
Incidence of adverse events
Will evaluate the number of participants experiencing treatment-related adverse events, classified by severity and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Observed toxicities will be summarized by type (organ affected or laboratory determination), severity, date of onset, duration, and attribution.
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University of California, Davis
Lead sponsor
National Cancer Institute (NCI)
Collaborator
ADC Therapeutics S.A.
Collaborator
