Loncastuximab Tesirine and Rituximab Followed by DA-EPOCH-R for Treating Patients With High-Risk Diffuse Large B-cell Lymphoma

Recruiting now · Phase 2

Conditions studied: Double-Expressor Lymphoma, High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangements, High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements

In brief

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.

Key facts

Study ID: NCT05600686
Run by: University of California, Davis
People needed: 24
Starts: 2023-05-24
Expected to finish: 2027-12-15
Last updated by the study team: 2026-06-30

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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

You may not qualify if…

Current/ prior use of:
Lymphoma treatment, except for:
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)
Other cancer therapies (e.g., prostate, breast hormonal-based therapy) per the principal investigator's discretion
Anthracycline greater than 50 mg/m\^2 (total lifetime) for a prior malignancy
Complementary and alternative medications (CAM) within 1 week prior to initiating study treatment
Treatment with any other investigational agent for any indication within 3 weeks prior to initiating study treatment
Loncastuximab tesirine or rituximab with progression within 6 months of initiating study treatment
Oral or intravenous (IV) antibiotics within 2 weeks prior to initiating study treatment. Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible
Live, attenuated influenza vaccine within 4 weeks prior to initiating study treatment
Immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor, such as anti-tumor necrosis factor [TNF] agents) within 14 days prior to initiating study treatment. The following are exceptions to this criterion:
Steroids
Bisphosphonate therapy for symptomatic hypercalcemia or for other reasons (e.g., bone metastasis or osteoporosis)
Known uncontrolled central nervous system (CNS) involvement by lymphoma, including leptomeningeal involvement
History of hypersensitivity to anti-CD19 antibodies, loncastuximab tesirine, or any agents used in DA-EPOCH-R
History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
History of allergic reactions attributed to compounds of similar chemical or biologic composition to other agents used in study
Clinically significant third space fluid accumulation (i.e., ascites requiring drainage or pleural effusion that is either requiring drainage or associated with shortness of breath)
Breastfeeding or pregnancy
Clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; or inherited liver disease
Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HbsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible
Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA)

Where it is running

University of California Davis Comprehensive Cancer Center — Sacramento, California, United States (enrolling)
UC San Diego Moores Cancer Center — San Diego, California, United States (enrolling)

Full record on ClinicalTrials.gov

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