Large B-cell Lymphoma, Relapse
Conditions
Brief summary
The purpose of this study is to determine whether combining Loncastuximab Tesirine with Epcoritamab is tolerable and effective for reducing and/or eliminating lymphoma cells in the body.
Interventions
DRUGEpcoritamab
Epcoritamab will be administered via subcutaneous injection at the following dose levels and schedule over a total of twelve cycles: * Cycle 1 Day 1: Step-up dose of 0.16 mg * Cycle 1 Day 8: Step-up dose of 0.80 mg * Cycle 1 Day 15: First full dose of 48 mg. * Cycles 2 through 4 Days 1, 8 and 15: 48 mg * Cycles 5 through 12 Days 1 and 15: 48 mg
DRUGLoncastuximab Tesirine
Loncastuximab will be administered intravenously (IV) at the following dose level and schedule over a total of four cycles: * Cycles 1 and 2 Day 1: 120 mcg/kg * Cycles 3 and 4 Day 1: 75 mcg/kg * Cycle 4 Day 22: 75 mcg/kg
Sponsors
University of Miami
ADC Therapeutics S.A.
Genmab
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Men and women aged 18 years or older at the time of signing informed consent. 2. Able and willing to sign the informed consent form (ICF). 3. Ability to comply with the trial protocol. 4. Relapsed/refractory (r/r) large B-cell lymphoma (LBCL) as determined by the local hematopathology laboratory from the following diagnoses by 2016 World Health Organization (WHO) classification of lymphoid neoplasms (Swerdlow et al., 2016): 1. LBCL or DLBCL, not otherwise specified (NOS) 2. High-grade B-cell lymphoma (NOS or double/triple hit \[technically classified in WHO 2016 as high-grade B-cell lymphoma (HGBCL), with Myc and B-cell lymphoma 2 (BCL2) and/or B-cell lymphoma 6 (BCL6) translocations\]) 3. Transformed from follicular lymphoma, marginal zone lymphoma (MZL), and nodular lymphocyte predominant Hodgkin lymphoma 4. Follicular lymphoma stage 3B 5. Primary mediastinal B-cell lymphoma previously treated with checkpoint inhibitor Note: Relapsed disease is defined as disease that has recurred ≥6 months after completion of therapy. Refractory disease is defined as disease that either progressed during therapy or progressed within 6 months (\<6 months) of completion of therapy. 5. Participants who have received at least one prior systemic therapy for LBCL including anti-cluster of differentiation 20 (anti-CD20) monoclonal antibody and anthracycline-containing therapy. 6. Measurable disease by 2014 Lugano Classification. (Participants who have measurable disease, defined as at least 1 bi-dimensionally measurable nodal lesion, defined as \>1.5 cm in its longest dimension, or at least 1 bi-dimensionally measurable extra nodal lesion, defined as \>1.0 cm in its longest dimension.) 7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 2. 8. Adequate hematologic, hepatic, and renal function tested within 6 weeks prior to the start of therapy (values must not be achieved with growth factors within 72 hs): 1. Absolute neutrophil count (ANC) ≥ 1.0 × 10\^9 cells/L 2. Hemoglobin ≥8.0 g/dL without blood transfusion in the past week 3. Platelet count ≥75 × 10\^9 platelets/L or ≥ 50 × 10\^9 platelets/L if bone marrow involvement or splenomegaly 4. Total bilirubin ≤1.5 × upper limit normal (ULN). Participants with documented history of Gilbert's syndrome and in whom total bilirubin elevations are accompanied by elevated indirect bilirubin are eligible (≤3x institutional ULN if lymphoma involvement of the liver). 5. Alanine transaminase (ALT)/aspartate aminotransferase (AST) ≤3.0 × ULN or ≤5 × ULN in the presence of liver involvement by lymphoma. * i. Creatinine within normal institutional limits, or calculated creatinine clearance ≥40 mL/min by the Cockcroft-Gault Equation or other institutional standard methods 9. Willingness to avoid pregnancy during the trial and for at least 12 months after the last dose of the trial intervention. 10. Patients with history of human immunodeficiency virus (HIV) are eligible, provided they are stable on anti-retroviral therapy, have cluster of differentiation 4 (CD4) count ≥200/µL, and have an undetectable viral load. Note: HIV test is optional. 11. Life expectancy of at least 12 weeks 12. For patients receiving glucocorticoid treatment at screening: treatment must be tapered down and administered with a maximum of 25 mg daily in the last 14 days before the first dose of epcoritamab.
Exclusion criteria
1. Primary central nervous system (CNS) lymphoma or known CNS involvement by lymphoma at screening as confirmed by magnetic resonance imaging (MRI)/computed tomography (CT) scan (brain) and, if clinically indicated, by lumbar puncture. 2. Prior treatment with anti-cluster of differentiation 19 (anti-CD19) chimeric antigen receptor T-cell (CAR-T) therapy 3. Prior exposure to bispecific T-cell engaging antiCD20XCD3 antibodies 4. Prior autologous or allogenic stem cell transplant 5. Known clinically significant pulmonary disease, including: 1. Pulmonary fibrosis affecting patient's exercise tolerance. 2. Chronic obstructive pulmonary disease (COPD) affecting patient's exercise tolerance. 6. Known clinically significant cardiac disease, including: 1. Onset of unstable angina pectoris within 6 months of signing ICF 2. Acute myocardial infarction within 6 months of signing ICF 3. Congestive heart failure (grade III or IV as classified by the New York Heart Association 7. Pregnant or breast feeding 8. Inadequate recovery from toxicity and/or complications from a major surgery before starting therapy. 9. Chronic or current active infectious disease (including severe acute respiratory syndrome (SARS) coronavirus 2 (CoV-2) requiring systemic antibiotics, antifungal, or antiviral treatment or any major episode of infection requiring treatment with intravenous (IV) antibiotics within 2 weeks of Day 1 of Cycle 1. 10. Exposure to a live vaccine within 30 days of administration or anticipation that a live attenuated vaccine will be required during the study. 1. Inactivated influenza vaccinations may be given during the influenza season. 2. An approved coronavirus disease 2019 (COVID-19) vaccine (messenger ribonucleic acid (mRNA), inactivated virus, and replication deficient viral vector vaccines) is allowed. 11. Active hepatitis B infection a. Patients who are hepatitis B surface antigen (HbsAg) negative and hepatitis B core antibody (HbcAb) positive must be negative for hepatitis B virus (HBV) polymerase chain reaction (PCR) to be eligible for study participation 12. Active hepatitis C infection a. Patients who are positive for hepatitis C virus (HCV) antibody must be negative for HCV by PCR to be eligible for study participation 13. Patient has no known active SARS-CoV-2 infection. If a subject has signs/symptoms suggestive of SARS-CoV-2 infection, the patient must have a negative molecular (eg, PCR) test or 2 negative antigen test results at least 24 hours apart. Note: SARS-CoV-2 diagnostic tests should be applied following local requirements/recommendations. Patients who do not meet SARS-CoV-2 infection eligibility criteria must be screen-failed and may only rescreen if the following have been met: * At least 10 days since first positive test result have passed in asymptomatic patients or at least 10 days since recovery, defined as resolution of fever without use of antipyretics and improvement in symptoms. 14. Patients with severe chronic pulmonary disease, or other serious medical condition which is likely to significantly impair the patient's ability to tolerate the study treatment. 15. Patients with seizure disorder requiring therapy with a last convulsion within two years from enrollment. 16. Patients with impaired decision-making capacity.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing Cytokine Release Syndrome (CRS)-related Toxicity after Epcoritamab Administration | Up to 14 months | The number of participants experiencing Cytokine Release Syndrome (CRS) toxicity associated with Epcoritamab therapy will be reported, including Grades 2, 3 and 4. CRS-related toxicity will be assessed according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria. |
| Number of Participants Experiencing Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS)-related Toxicity | Up to 14 months | The number of participants experiencing Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS)-related toxicity including Grades 2, 3 and 4. ICANS-related toxicity will be assessed according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria. |
| Number of Participants Experiencing Neurologic Toxicities Associated with Epcoritamab | Up to 14 months | The number of participants experiencing neurologic toxicities associated with Epcoritamab therapy will be reported, including Grades 2, 3 and 4. Neurologic toxicities will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, per physician discretion. |
| Number of Participants Experiencing Fluid Accumulation Associated with Loncastuximab | Up to 31 weeks | The number of participants experiencing fluid accumulation associated with Loncastuximab therapy will be reported, including Grades 2, 3 and 4. Fluid accumulation toxicities will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, per physician discretion. |
| Number of Participants Experiencing Hepatotoxicity Associated with Loncastuximab | Up to 31 weeks | The number of participants experiencing hepatotoxicity (liver-related toxicity) associated with Loncastuximab therapy including Grades 2, 3 and 4 toxicity. Hepatotoxicity will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, per physician discretion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | Up to 36 months | Overall response rate is defined as the number of participants with complete metabolic response (CMR) or partial metabolic response (PMR) as the best response. Response will be assessed according to Lugano 2014 criteria. |
| Partial Metabolic Response (PMR) Rate | Up to 36 months | PMR rate is defined as the number of participants with partial metabolic response (PMR) as the best response according to Lugano 2014 criteria. |
| Progression-Free Survival (PFS) | Up to 36 months | PFS is defined as the elapsed time in months from the start of treatment until disease progression or death, whichever is earlier. Participants who remain alive without progression will be censored at the last documented disease assessment date. Response will assessed according to Lugano 2014 criteria. |
| Overall Survival (OS) | Up to 36 months | OS is defined as the elapsed time in months from the start of treatment until death from any cause. Alive participants will be censored at the last date known to be alive. |
Countries
United States
Contacts
CONTACTJuan Alderuccio, MD
PRINCIPAL_INVESTIGATORJuan Alderuccio, MD
University of Miami
Outcome results
None listed