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About
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.
Full description
PRIMARY OBJECTIVE:
I. To obtain a preliminary estimate of the anti-tumor activity of loncastuximab tesirine and rituximab (lonca-R) in newly diagnosed double-expressor lymphoma (DEL) and double-hit lymphoma (DHL).
SECONDARY OBJECTIVES:
I. To obtain additional efficacy measures of lonca-R in newly diagnosed DEL and DHL.
II. To assess safety and tolerability of lonca-R followed by dose-adjusted doxorubicin, etoposide, vincristine, cyclophosphamide, and prednisone (DA-EPOCH-R) as coded by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.
OUTLINE:
Patients receive rituximab intravenously (IV), loncastuximab tesirine IV, etoposide IV, doxorubicin IV, vincristine IV, prednisone orally (PO), and cyclophosphamide IV on study. Patients also undergo collection of blood samples and bone marrow aspiration and biopsy at screening and computed tomography (CT) or positron emission tomography (PET)/CT at screening, throughout the study, and during follow up.
Enrollment
Sex
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Volunteers
Inclusion criteria
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:
Exclusion criteria
Current/ prior use of:
Lymphoma treatment, except for:
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:
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
Documented eczema, psoriasis, or lichen simplex chronicus of vitiligo with dermatologic manifestations (e.g., patients with psoriatic arthritis would be excluded), unless the following apply:
Known active tuberculosis (TB)
Severe infections within 4 weeks prior to initiating study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
Major surgical procedure within 28 days prior to initiating study treatment or anticipation of need for a major surgical procedure during the course of the study
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Primary purpose
Allocation
Interventional model
Masking
24 participants in 1 patient group
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Central trial contact
Joseph M Tuscano
Data sourced from clinicaltrials.gov
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