A Phase 2 Study of Loncastuximab Tesirine and Rituximab (Lonca-R) Followed by DA-EPOCH-R in Previously Untreated High-Risk Diffuse Large B-Cell Lymphoma
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%)
• Life expectancy \>= 6 months
• Leukocytes \>= 2,500/uL
• Absolute neutrophil count \>= 1,000/uL
• Platelets \>= 100,000/uL
• Hemoglobin \>= 8 g/dL
• Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (however, patients with known Gilbert disease who have serum bilirubin level =\< 3 x ULN may be enrolled)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x ULN (AST and/or ALT =\< 5 x ULN for patients with liver involvement)
• Alkaline phosphatase =\< 2.5 x ULN (=\< 5 x ULN for patients with documented liver involvement or bone metastases)
• Creatinine clearance \>= 30 mL/min by Cockcroft-Gault
• Activated partial thromboplastin time (aPTT) =\< 1.5 x ULN (This applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation, such as low-molecular-weight heparin or warfarin, should be on a stable dose)
• Transthoracic echocardiography (TTE) or multigated acquisition scan (MUGA) ejection fraction greater than 40%
• Women of child-bearing potential (WOCBP) must agree to use a highly effective method of contraception from the time of giving informed consent until at least 10 months after the last dose of study drug. Men with female partners who are of childbearing potential must agree to use a highly effective method of contraception from the time of giving informed consent until at least 7 months after the last dose of study drug
• Ability to understand and the willingness to sign a written informed consent document
• Human immunodeficiency virus (HIV) infected patients:
‣ No history of acquired immunodeficiency syndrome (AIDS)-defining conditions other than lymphoma or history of CD4+ T-cells below 200/mm\^3 prior to beginning combination anti-retroviral therapy (ART)
⁃ Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
⁃ At time of study entry CD4+ T-cells must have recovered from prior lymphoma therapy to \>= 250/mm\^3
⁃ At the time of study entry, the HIV viral load must be undetectable by standard laboratory assay
⁃ During prior lymphoma therapy, patients must not have experienced documented infections attributed to the HIV positive (+) status
⁃ No history of non-adherence to ART and willing to adhere to ART while on study
⁃ Antiretroviral drugs with overlapping or similar toxicity profiles as study agents not allowed