Loncastuximab Tesirine as Consolidation Therapy for the Treatment of Relapsed or Refractory Large B-cell Lymphoma
This phase II trial tests whether loncastuximab tesirine works to control large B-cell lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Loncastuximab tesirine is a monoclonal antibody, called loncastuximab, linked to a chemotherapy agent called tesirine. Loncastuximab attached to CD19 positive cancer cells in a targeted way and delivers tesirine to kill them. Giving loncastuximab tesirine may kill more cancer cells in patients with large B-cell lymphoma.
Inclusion Criteria
- Relapsed or refractory diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, transformed indolent B-cell lymphomas and high-grade B-cell lymphoma
- Receive standard of care treatment with an Food and Drug Administration (FDA)-approved anti-CD19 autologous CAR T-cell product, outside of a clinical trial
- >= 18 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
- Achievement of PR according to Lugano 2014 response criteria 30 days after CAR T-cell therapy
- At least 30 days must have elapsed since CAR T-cell therapy infusion
- No evidence of CD19 expression after CAR T-cell therapy infusion is required for enrollment
- No additional anti-tumoral therapy, with the exclusion of palliative radiotherapy, must have been received after CAR T-cell therapy
- Absolute neutrophil count (ANC) of >= 1.0 x 10^9/L without growth factor support for 7 days prior to screening assessment
- Platelet count of >= 50 x 10^9/L without transfusion for 3 days prior to screening assessment
- Creatinine clearance (as estimated by Cockcroft Gault) >= 30 mL/min
- Serum alanine transaminase (ALT), aspartate transaminase (AST) or gamma glutamyl transferase (GGT) =< 2.5 upper limit of normal (ULN)
- Total bilirubin =< 2 mg/dL, except in subjects with Gilbert’s syndrome
- Cardiac ejection fraction >= 45% with no evidence of clinically significant pericardial effusion
- Baseline oxygen saturation > 92% on room air
- No evidence or suspicion of lymphoma actively involving the central nervous system (CNS)
- Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential)
- Resolution of any previous cytokine release syndrome (CRS) and/or immune effector cell associated neurotoxicity syndrome (ICANS) to grade 0.
Exclusion Criteria
- 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)
- History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g. prostate, cervix, bladder, breast) unless disease free for at least 12 months
- History of Richter’s transformation of chronic lymphocytic leukemia (CLL)
- Treatment with CAR T-cell therapy on clinical trial as immediate treatment before enrollment
- Prior treatment with lonca
- Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management. Simple urinary tract infection (UTI) and uncomplicated bacterial pharyngitis are permitted if responding to active treatment and after consultation with the principal investigator
- Known history of infection with human immunodeficiency virus (HIV) or hepatitis B (HBsAg positive) or hepatitis C virus (antiHCV positive). A history of HIV, hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative polymerase chain reaction (PCR) and/or nucleic acid testing.
- Subjects with active cardiac atrial or cardiac ventricular lymphoma involvement
- History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment
- Primary immunodeficiency
- History of autoimmune disease (e.g. Crohns, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring active systemic immunosuppression/systemic disease modifying agents within the last 2 years
- History of clinically significant deep vein thrombosis or pulmonary embolism within 1 month of enrollment per investigators discretion
- Any medical condition likely to interfere with assessment of safety or efficacy of study treatment
- History of severe immediate hypersensitivity reaction to any of the agents used in this study
- Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the peroxisome biogenesis disorder (PBD) on the fetus or infant
- Subjects of both genders who are not willing to practice birth control. Women of childbearing potential must use a highly effective method of contraception (hormonal birth control such as birth control pills, intravaginal ring, skin patch, implant or injection, intrauterine device or surgical sterilization) until 9 months after last dose of lonca, and men with female partners who are of childbearing potential should use a condom when sexually active until 6 months after the last dose of lonca
- In the investigator’s judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation trial treatments
Additional locations may be listed on ClinicalTrials.gov for NCT05464719.
Locations matching your search criteria
United States
Texas
Houston
PRIMARY OBJECTIVE:
I. To evaluate the efficacy of loncastuximab tesirine (lonca) as consolidation therapy in patients with relapsed or refractory large B-cell lymphoma (LBCL) who achieve partial response (PR) after CAR T-cell therapy.
SECONDARY OBJECTIVE:
I. To evaluate safety and tolerability of lonca as consolidation therapy in patients with relapsed or refractory LBCL who achieve PR after CAR T-cell therapy.
EXPLORATORY OBJECTIVE:
I. To determine the pharmacodynamic effects and investigate biomarkers of response and resistance of this novel consolidation therapy.
OUTLINE:
Patients receive loncastuximab tesirine intravenously (IV) over 30-60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiogram during screening, and computed tomography (CT) scan, positron emission tomography (PET) scan or magnetic resonance imaging (MRI) throughout the study.
After completion of study treatment, patients are followed up every 12 weeks for 1 year, and then every 24 weeks for up to 3 years after the last dose of study drug.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationM D Anderson Cancer Center
Principal InvestigatorPaolo Strati
- Primary ID2022-0147
- Secondary IDsNCI-2022-05750
- ClinicalTrials.gov IDNCT05464719