LONCASTUXIMAB TESIRINE for Diffuse large B-cell lymphoma (DLBCL) | High-grade B-cell lymphoma (HGBCL)

Inclusion criteria

• {"criterion_text":"- 1. Male or female, aged ≥18 years.\n- 2. Willing and able to give written, informed consent.\n- 3. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.\n- 4. Histologically confirmed DLBCL or large B cell lymphoma (at last relapse) as defined by the 2016 WHO classification, including one of the following: • DLBCL, Not Otherwise Specified (NOS) • Transformed DLBCL from indolent lymphoma • HGBCL with MYC and BCL2 and/or BCL6 rearrangements (double/triple hit)\n- 5. Patients failing CAR T-cell therapy, defined as: a. Progressive disease (PD) at any time b. Partial Remission (PR) or stable disease (SD) at 3 months after CAR T-cell infusion.\n- 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 tumour is not FDG-avid on screening PET-CT.\n- 7. Previous treatment with loncastuximab tesirine is allowed, provided that the patient was in CR or PR at the time of drug withdrawal.\n- 8. Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test within 7 days prior to start of study drug (C1D1) for women of childbearing potential.\n- 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.\n- 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. • Known history of LVEF ≥50% unless the institutional lower limit of normal is lower. • Baseline oxygen saturation >92% on room air and ≤Grade 1 dyspnoea.\n- 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. • Haemoglobin ≥9.0 g/dL • Platelets ≥50 × 10^6/dL"}

Exclusion criteria

• {"criterion_text":"- 1. Known history of hypersensitivity to or positive serum human antidrug antibody (ADA) to a CD19 antibody.\n- 2. Females who are pregnant or lactating.\n- 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.\n- 4. Lymphoma with active CNS involvement at the time of screening, including leptomeningeal disease.\n- 5. Bulky disease, defined as largest tumour diameter >10 cm.\n- 6. Known seropositive and requiring anti-viral therapy for human immunodeficiency (HIV) virus, hepatitis B virus (HBV), or hepatitis C virus (HCV).\n- 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)\n- 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.\n- 9. Active autoimmune disease, motor neuropathy considered of autoimmune origin, and other central nervous system (CNS) autoimmune disease.\n- 10. History of Steven's Johnson's syndrome or toxic epidermal necrolysis syndrome.\n- 11. Major surgery, radiotherapy, chemotherapy or other antineoplastic therapy within 14 days prior to start of study drug (C1D1), except shorter if approved by the Sponsor.\n- 12. Planned live vaccine administration after starting study drug (C1D1).\n- 13. Use of any other experimental medication within 14 days prior to start of study drug (C1D1).\n- 14. Failure to recover to Grade ≤1 (Common Terminology Criteria for Adverse Events version 5.0 [CTCAE v5.0]) from acute nonhematologic toxicity (Grade ≤2 neuropathy or alopecia) due to previous therapy prior to screening.\n- 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."}

Primary endpoints

• {"endpoint_text":"- Overall response rate (ORR) defined as patients in achieving a best overall response of complete response (CR) or partial response (PR) to study treatment, according to the 2014 Lugano Classification","definition_or_measurement_approach":"Defined as patients achieving a best overall response of complete response (CR) or partial response (PR) to study treatment, according to the 2014 Lugano Classification"}

Secondary endpoints

• {"endpoint_text":"- • 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\n- • Overall survival (OS) defined as the time between first dose administration and death from any cause\n- • Duration of Response (DOR) defined as the time from first documentation of response to recurrence or progression by independent central review, or death\n- • Frequency and severity of adverse events (AEs) and severeserious adverse events (SAEs)\n- • 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","definition_or_measurement_approach":"PFS: time between first dose and first documentation of recurrence/progression by independent central review or death; OS: time between first dose and death from any cause; DOR: time from first documentation of response to recurrence/progression by independent central review or death; safety: frequency and severity of AEs/SAEs; exploratory: correlations of serum markers (LDH, CRP, ferritin) and plasma ctDNA changes with efficacy endpoints."}

Italy

Earliest CTIS Part Ii Submission Date

06-08-2024

Latest Decision Or Authorization Date

16-01-2026

Processing Time Days

528

Number Of Sites

8

Number Of Participants

50

Primary sponsor

Full Name

Humanitas Mirasole S.p.A.

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy

Contract research organisations

Name

Clinical Research Technology S.r.l.

Responsibilities

sponsorDuties codes: 1,12,5,6,7,8; contact email: lorely@cr-technology.com

Third parties

• {"country":"Italy","full_name":"Clinical Research Technology S.r.l.","duties_or_roles":"sponsorDuties codes: 1,12,5,6,7,8","organisation_type":"Pharmaceutical company"}