Patients affected by relapsed/refractory DLBCL or HGBCL failing CAR T-cell therapy MedDRA version: 23.1 Level: LLT Classification code 10084346 Term: B-cell non-Hodgkin's lymphoma System Organ Class: 100000004864
Conditions
Interventions
Product Name: Zynlonta
Product Code: [ADCT-402]
Pharmaceutical Form: Powder for infusion
INN or Proposed INN: Loncastuximab Tesirine
CAS Number: 1879918-31-6
Current Sponsor code: Loncastuximab tesiri
Sponsors
IRCCS ISTITUTO CLINICO HUMANITAS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female, aged =18 years. 2. Willing and able to give written, informed consent. 3. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2. 4. Histologically confirmed DLBCL and large B cell lymphoma (at last relapse) subsets as defined by the 2016 WHO classification, including: • DLBCL, Not Otherwise Specified (NOS) • Transformed DLBCL from indolent lymphoma • HGBCL with MYC and BCL2 and/or BCL6 rearrangements (double/triple hit) 5. Patients failing CAR T-cell therapy, defined as: • Stable disease (SD) 1 month after CAR T-cell infusion • Progressive disease (PD) at any time • Partial Remission (PR) at 6 months after CAR T-cell infusion. 6. Measurable disease as defined by the 2014 Lugano Classification as assessed by positron-emission tomography (PET)- computed tomography (CT) or by CT or MRI if tumor is not FDG-avid on screening PET-CT. 7. Previous treatment with loncastuximab tesirine is allowed, provided that the patient was in CR or PR at the time of drug withdrawal. 8. Negative beta-human chorionic gonadotropin (ß-HCG) pregnancy test within 7 days prior to start of study drug (C1D1) for women of childbearing potential. 9. Women of childbearing potential must agree to use a highly effective method of contraception from the time of giving informed consent until at least 9 months after the last dose of loncastuximab tesirine. Men with female partners who are of childbearing potential must agree that they will use a highly effective method of contraception from the time of giving informed consent until at least 6 months after the patient receives his last dose of loncastuximab tesirine. 10. Adequate renal, hepatic, pulmonary, and cardiac function defined as: • Creatinine clearance =40 ml/min. • Serum alanine aminotransferase / aspartate aminotransferase =2.5 x ULN. • Total bilirubin =1.5 x ULN, except in subjects with Gilbert's syndrome. • LVEF =50% unless the institutional lower limit of normal is lower. • Baseline oxygen saturation >92% on room air and =Grade 1 dyspnea. 11. Adequate Bone Marrow (BM) function without requiring ongoing blood product or granulocyte-colony stimulating factor support (GCSF) and meeting the following criteria: • Absolute neutrophil count =1.0 × 10^6/dL. • Hemoglobin =9.0 g/dL • Platelets =50 × 10^6/dL Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 25 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
Exclusion criteria: 1. Known history of hypersensitivity to or positive serum human antidrug antibody (ADA) to a CD19 antibody. 2. Females who are pregnant or lactating. 3. Active second primary malignancy other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy that the Sponsor's medical monitor and Investigator agree and document should not be exclusionary. 4. Lymphoma with active CNS involvement at the time of screening, including leptomeningeal disease. 5. Bulky disease, defined as largest tumor diameter >10 cm. 6. Known seropositive and requiring anti-viral therapy for human immunodeficiency (HIV) virus, hepatitis B virus (HBV), or hepatitis C virus (HCV). 7. 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) 8. Significant medical comorbidities, including but not limited to, uncontrolled hypertension (blood pressure =160/100 mm Hg repeatedly), unstable angina, congestive heart failure (greater than New York Heart Association class II), electrocardiographic evidence of acute ischemia, coronary angioplasty or myocardial infarction within 6 months prior to screening, uncontrolled atrial or ventricular cardiac arrhythmia, poorly controlled diabetes, or severe chronic pulmonary disease. 9. Active autoimmune disease, motor neuropathy considered of autoimmune origin, and other central nervous system (CNS) autoimmune disease. 10. History of Steven's Johnson's syndrome or toxic epidermal necrolysis syndrome. 11. Major surgery, radiotherapy, chemotherapy or other anti-neoplastic therapy within 14 days prior to start of study drug (C1D1), except shorter if approved by the Sponsor. 12. Planned live vaccine administration after starting study drug (C1D1). 13. Use of any other experimental medication within 14 days prior to start of study drug (C1D1). 14. Failure to recover to Grade =1 (Common Terminology Criteria for Adverse Events version 5.0 [CTCAE v5.0]) from acute non-hematologic toxicity (Grade =2 neuropathy or alopecia) due to previous therapy prior to screening. 15. Any other significant medical illness, abnormality, or condition that would, in the Investigator’s judgment, make the patient inappropriate for study participation or put the patient at risk.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Assess the efficacy of loncastuximab tesirine as measured by overall response rate (ORR) in DLBCL and HGBCL patients failing CAR-T cell therapy;Secondary Objective: Secondary Objectives •Evaluate survival outcomes after Loncastuximab Tesirine •Evaluate the safety of loncastuximab tesirine Exploratory Objectives •Assess the changes in blood serum markers of disease and inflammation during the study course •Explore the correlation between clinical activity and changes in plasma circulating tumor DNA (ctDNA) during the study course;Primary end point(s): Tasso di risposta globale (ORR) definito come la porzione di pazienti che raggiungono la migliore risposta globale al trattamento di studio, in termini di risposta completa (CR) o risposta parziale (PR) secondo la Classificazione Lugano 2014;Timepoint(s) of evaluation of this end point: 6 months since start of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary • Progression-free survival (PFS) defined as the time between first dose administration and the first documentation of recurrence or progression by independent central review, or death • Overall survival (OS) defined as the time between first dose administration and death from any cause • Duration of Response (DOR) defined as the time from first documentation of response to recurrence or progression by independent central review, or death • Frequency and severity of adverse events (AEs) and severeserious adverse events (SAEs) Exploratory • Relationship between blood serum markers of disease and inflammation (LDH, CRP, ferritin) and selected efficacy endpoints • Relationship between changes in plasma ctDNA and selected efficacy endpoints;Timepoint(s) of evaluation of this end point: • End of study • End of study • End of study + 2 years since the end of study • Continuosly during the trial | — |
Countries
Italy
Contacts
Public ContactClinical Operations
Clinical Research Technology
Outcome results
None listed