RECRUITING

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

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Conditions

Double-Expressor LymphomaHigh Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 RearrangementsHigh Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 RearrangementsHigh Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2023-05-24
Study Completion:2028-02-01
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT05600686

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * 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)
  2. * Measurable disease by CT or PET/CT scan, with one or more sites of disease \>= 1.5 cm in longest dimension
  3. * Age \>= 18 years at time of consent
  4. * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
  5. * Life expectancy \>= 6 months
  6. * Leukocytes \>= 2,500/uL
  7. * Absolute neutrophil count \>= 1,000/uL
  8. * Platelets \>= 100,000/uL
  9. * Hemoglobin \>= 8 g/dL
  10. * 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)
  11. * 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)
  12. * Alkaline phosphatase =\< 2.5 x ULN (=\< 5 x ULN for patients with documented liver involvement or bone metastases)
  13. * Creatinine clearance \>= 30 mL/min by Cockcroft-Gault
  14. * 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)
  15. * Transthoracic echocardiography (TTE) or multigated acquisition scan (MUGA) ejection fraction greater than 40%
  16. * 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
  17. * Ability to understand and the willingness to sign a written informed consent document
  18. * Human immunodeficiency virus (HIV) infected patients:
  19. * 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)
  20. * Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  21. * At time of study entry CD4+ T-cells must have recovered from prior lymphoma therapy to \>= 250/mm\^3
  22. * At the time of study entry, the HIV viral load must be undetectable by standard laboratory assay
  23. * During prior lymphoma therapy, patients must not have experienced documented infections attributed to the HIV positive (+) status
  24. * No history of non-adherence to ART and willing to adhere to ART while on study
  25. * Antiretroviral drugs with overlapping or similar toxicity profiles as study agents not allowed
  1. * Current/ prior use of:
  2. * Lymphoma treatment, except for:
  3. * 1 cycle of DA-EPOCH-R or rituximab, cyclophosphamide, doxorubicin (Adriamycin) vincristine (Oncovin) and prednisolone (R-CHOP)
  4. * Radiotherapy \> 2 weeks of initiating study treatment
  5. * Nitrosoureas or mitomycin C \> 6 weeks of initiating study treatment
  6. * Steroid treatment for DLBCL or steroid monotherapy to stabilize disease while awaiting fluorescence in situ hybridization (FISH)
  7. * Other cancer therapies (e.g., prostate, breast hormonal-based therapy) per the principal investigator's discretion
  8. * Anthracycline greater than 50 mg/m\^2 (total lifetime) for a prior malignancy
  9. * Complementary and alternative medications (CAM) within 1 week prior to initiating study treatment
  10. * Treatment with any other investigational agent for any indication within 3 weeks prior to initiating study treatment
  11. * Loncastuximab tesirine or rituximab with progression within 6 months of initiating study treatment
  12. * 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
  13. * Live, attenuated influenza vaccine within 4 weeks prior to initiating study treatment
  14. * 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:
  15. * Steroids
  16. * Bisphosphonate therapy for symptomatic hypercalcemia or for other reasons (e.g., bone metastasis or osteoporosis)
  17. * Known uncontrolled central nervous system (CNS) involvement by lymphoma, including leptomeningeal involvement
  18. * History of hypersensitivity to anti-CD19 antibodies, loncastuximab tesirine, or any agents used in DA-EPOCH-R
  19. * History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  20. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to other agents used in study
  21. * 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)
  22. * Breastfeeding or pregnancy
  23. * Clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; or inherited liver disease
  24. * 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
  25. * Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA)
  26. * 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:
  27. * Affected skin covers less than 10% of body surface area (BSA)
  28. * Disease is well controlled at baseline and only requires low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%)
  29. * No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation \[PUVA\], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
  30. * Known active tuberculosis (TB)
  31. * Severe infections within 4 weeks prior to initiating study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
  32. * 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
  33. * 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

Contacts and Locations

Study Contact

Joseph M Tuscano
CONTACT
916-734-3771
jtuscano@ucdavis.edu

Principal Investigator

Joseph M Tuscano
PRINCIPAL_INVESTIGATOR
University of California, Davis

Study Locations (Sites)

University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
United States

Collaborators and Investigators

Sponsor: Joseph Tuscano

  • Joseph M Tuscano, PRINCIPAL_INVESTIGATOR, University of California, Davis

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-05-24
Study Completion Date2028-02-01

Study Record Updates

Study Start Date2023-05-24
Study Completion Date2028-02-01

Terms related to this study

Additional Relevant MeSH Terms

  • 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