Loncastuximab Tesirine and Rituximab as Bridging Therapy Before Standard-of-care CAR-T Therapy in Patients With Large B-cell Lymphoma (CORAL)

Inclusion Criteria

• •Subject aged ≥ 18 years.
• •Intended to receive commercial CD19-directed CAR-T cell therapy (axi-cel and liso-cel).
• •Need for bridging therapy as deemed clinically necessary by the treating physician.
• •Relapsed or refractory DLBCL, tFL or PMBCL as defined by the 2016 World Health Organization classification (including patients with DLBCL transformed from indolent lymphoma), or high-grade B-cell lymphoma (HGBL), not otherwise specified, and HGBL with MYC and BCL2 and/or BCL6 rearrangements.
• •--Relapsed (disease that has recurred following a response) or refractory (disease that failed to respond to prior therapy) disease following at least one multi-agent systemic treatment regimen.
• •Measurable disease as defined by the 2014 Lugano Classification as assessed by positron-emission tomography (PET)- computed tomography (CT) or by CT or magnetic resonance imaging (MRI) if the tumor is not fluorodeoxyglucose (FDG)-avid on screening PET-CT.
• •ECOG Performance Status ≤ 2.
• •Time between prior anticancer therapy and first dose of lonca-R as below
• •* Autologous hematopoietic cell transplantation - At least 30 days
• •* Allogeneic hematopoietic cell transplantation - At least 60 days
• •* Cytotoxic chemotherapy - At least 21 days
• •* Non-cytotoxic chemotherapy (e.g., small molecule inhibitor) - At least 14 days
• •Adequate organ function as defined as:
• •* Hematologic:
• •* Absolute neutrophil count (ANC) ≥ 1000/mm3
• •* Platelet count ≥ 75,000/mm3
• •* Hemoglobin ≥ 8 g/dL
• •* Hepatic:
• •* Bilirubin ≤1.5 x upper limit of normal (ULN) or ≤3 x ULN with document liver involvement and/ or Gilbert's disease
• •* Transaminases (AST or ALT) ≤ 3 x ULN or ≤ 5 x ULN with documented liver involvement
• •* Renal:
• •* Estimated creatinine clearance ≥ 60 mL/min by Cockcroft-Gault formula.
• •For female subjects: Negative pregnancy test or evidence of post-menopausal status. The post-menopausal status will be defined as having been amenorrheic for 12 months without an alternative medical cause or having undergone surgical sterilization (bilateral oophorectomy or hysterectomy). The following age-specific requirements apply:
• •* Women \< 50 years of age:
• •* Amenorrheic for ≥ 12 months following cessation of exogenous hormonal treatments; and
• •* Luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution; or
• •* Underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
• •* Women ≥ 50 years of age:
• •* Amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments; or
• •* Had radiation-induced menopause with last menses \>1 year ago; or
• •* Had chemotherapy-induced menopause with last menses \>1 year ago; or
• •* Underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy).
• •Female subjects of childbearing potential and male subjects with a sexual partner of childbearing potential must agree to use a highly effective method of contraception and the lactation requirements as described in Sections 5.41.1 and 5.4.2.
• •Subjects or their legal representatives must be able to read, understand, and provide informed consent to participate in the trial.
• •Willing and capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol