LONCASTUXIMAB TESIRINE for Mantle cell lymphoma

Inclusion criteria

• {"criterion_text":"- Histologically documented diagnosis of MCL as defined in the 2017 edition of the World Health Organization (WHO) classification;\n- ECOG/WHO performance status ≤ 2 (unless MCL-related);\n- The following laboratory values at screening (unless due to bone marrow involvement by lymphoma): - Absolute neutrophil count (ANC)  1.0×109/L, - Platelets  75.000/mm3, - Creatinine clearance ≥ 40 mL/min (Cockcroft-Gault formula); - Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x ULN; - Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert’s syndrome or of non-hepatic origin);\n- Subject understands and voluntarily signs an informed consent form approved by the National Ethic Committee (NEC), prior to the initiation of any screening or study-specific procedures\n- Subject must be able to adhere to the study visit schedule and other protocol requirements;\n- Life expectancy ≥ 3 months;\n- Women of childbearing potential (WOCBP) must agree to use effective contraception if sexually active. This applies for the time period between signing of the informed consent form and at least 10 months after last loncastuximab tesirine (ADCT-402) dose. Men with female partners who are of childbearing potential must agree to use effective contraception if sexually active. This applies for the time period between signing of the informed consent form and at least 7 months after last loncastuximab tesirine (ADCT-402) dose.\n- Age ≥ 18 and < 85 years\n- Relapsed/Refractory disease after one, two, three or four lines of treatment;\n- Bendamustine-naive or relapsed after at least one year after the last cycle of a bendamustine-containing regimen\n- Previous treatment with BTKi monotherapy or BTKi containing regimens with R/R disease; and/or patients who discontinued BTKi monotherapy or BTKi containing regimens for adverse events and have active disease necessitating treatment;\n- Previous treatment with any anti-CD19 agents is allowed (included CAR-T treatment) If previous anti-CD19 treatment has occurred, tissue CD19 expression must be assessed by histology or flow cytometry.\n- Venetoclax treated patients are allowed;\n- Stem cell transplant eligible patients are allowed;\n- Measurable nodal or extranodal disease ≥ 1.5 cm in longest diameter, and measurable in 2 perpendicular dimensions. Note: Patients with bone marrow involvement only are eligible. In case of bone marrow infiltration only, bone marrow aspiration and biopsy are mandatory for all staging evaluations;"}

Exclusion criteria

• {"criterion_text":"- Subjects who have received a bendamustine containing regimen and relapsed less than one year after the end of treatment\n- Evidence of other clinically significant uncontrolled condition(s) including, but not limited to: - Uncontrolled and/or active systemic infection (viral including COVID 19, bacterial or fungal); - Chronic or acute hepatitis B (HBV) or hepatitis C (HCV) requiring treatment. Note: subjects with serologic evidence of prior vaccination to HBV (i.e., HBsAg negative, HBsAb positive and HBcAb negative) or positive HBcAb from previous infection or intravenous immunoglobulins (IVIG) may participate; inactive carriers (HBsAg positive with undetectable HBV DNA) are eligible. Patients with presence of HCV antibody are eligible only if PCR result are negative for HCV RNA;\n- HIV seropositivity;\n- Lymphoma with active CNS involvement at the time of screening, including leptomeningeal disease;\n- Congenital long QT syndrome or a corrected QTcF interval of >480 msec at screening (unless secondary to pacemaker or bundle branch block);\n- 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;\n- If female, the patient is pregnant or breast-feeding.\n- Known history of hypersensitivity to human antibodies;\n- Allogenic stem cell transplant within 6 months prior to start of first study drug;\n- Allogenic stem cell transplant with active / uncontrolled graft-versus-host disease;\n- More than four lines of previous treatment (autologous stem cell transplant performed as part of consolidation to a previous line of therapy should not be considered as a line of therapy);\n- Active second malignancy in the last three years other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or any other tumor that the Sponsor and Coordinating Investigator agree and document should not be considered preclusive to participate in the study;\n- Major surgery or any anticancer therapy including chemotherapy, immunotherapy, radiotherapy, investigational therapy, including targeted small molecule agents within 14 days prior to start of study drug (R-BAC). A shorter interval in special settings must be approved by the Sponsor and/or Investigator;\n- Cardiovascular disease (NYHA class ≥2);\n- Significant history of neurologic, psychiatric, endocrinological, metabolic, immunologic, or hepatic disease that would preclude participation in the study or compromise ability to give informed consent;"}

Primary endpoints

• {"endpoint_text":"- 12-month Progression-Free Survival (PFS), defined as the time between the date of enrollment and the first documentation of recurrence, progression or death from any cause; responding patients and patients who are lost to follow up will be censored at their last assessment date. PFS will be assessed on an ITT (Intention to Treat) basis.","definition_or_measurement_approach":"PFS defined as time between enrollment date and first documentation of recurrence, progression or death from any cause; responding patients and patients lost to follow-up censored at last assessment date; assessed on an ITT basis."}

Secondary endpoints

• {"endpoint_text":"- Overall survival (OS), defined as the time between the start of treatment until death from any cause; patients who are lost at follow up will be censored at their last assessment date. Analysis will be on an ITT basis.","definition_or_measurement_approach":"OS defined as time between start of treatment and death from any cause; patients lost to follow-up censored at last assessment; ITT analysis."}
• {"endpoint_text":"- Rate of conversion from partial response to complete response (PR to CR) and from stable disease (SD) to PR/CR rate, assessed by comparing responses prior to and after loncastuximab tesirine.","definition_or_measurement_approach":"Conversion rates assessed by comparing response status before and after loncastuximab tesirine administration."}
• {"endpoint_text":"- Overall Response Rate (ORR), CR, PR and SD rate, will be defined according to Lugano 2014 criteria. The best overall response will be defined as the best response between the date of beginning of therapy and the last restaging. Patients without response assessment (due to whatever reason) will be considered as non-responders.","definition_or_measurement_approach":"ORR/CR/PR/SD defined per Lugano 2014; best overall response is best response between therapy start and last restaging; patients without assessment considered non-responders."}
• {"endpoint_text":"- Duration of Response (DOR), defined as the time from the first documentation of tumor response (CR/PR) to disease progression or death according to Lugano 2014 criteria. Analysis will be on an ITT basis","definition_or_measurement_approach":"DOR defined as time from first documentation of CR/PR to progression or death per Lugano 2014; ITT analysis."}
• {"endpoint_text":"- Event-Free Survival (EFS), defined as the time from start of treatment to disease progression, death, or discontinuation of treatment for any reason (e.g. toxicity, patient preference), or initiation of a new treatment without documented progression. Analysis will be on an ITT basis.","definition_or_measurement_approach":"EFS defined as time from treatment start to progression, death, treatment discontinuation for any reason, or start of a new treatment without documented progression; ITT analysis."}
• {"endpoint_text":"- MRD negativity rate, defined as the rate of MRD (Minimal Residual Disease) negativity after induction treatment (2 x R-BAC), at the end of consolidation with the loncastuximab tesirine and after 6 and 12 months after the end of consolidation.","definition_or_measurement_approach":"MRD negativity rate measured after induction (2x R-BAC), at end of consolidation, and at 6 and 12 months post-consolidation."}
• {"endpoint_text":"- Rate of Adverse Events Any grade III or higher toxicities will be recorded and classified according to the definitions of the current version of the NCI Common Terminology Criteria for Adverse Events (CTCAE). Toxicity events will be determined by the incidence of severe, life-threatening (CTCAE grade 3, 4 and 5) and/or serious adverse events (SAEs) commencing after the first induction dose or at any time during therapy.","definition_or_measurement_approach":"Adverse events graded per NCI CTCAE current version; incidence of grade ≥3 and SAEs recorded from first induction dose or anytime during therapy."}

Italy

Earliest CTIS Part Ii Submission Date

13-06-2024

Latest Decision Or Authorization Date

07-08-2024

Processing Time Days

55

Number Of Sites

21

Number Of Participants

49

Primary sponsor

Full Name

Fondazione Italiana Linfomi Ets

Organisation Type

Patient organisation/association

Country Of Registered Address

Italy