loncastuximab tesirine and rituximab as bridging therapy prior to standard-of-care cd19 car t-cell therapy in patients with large b-cell lymphoma

Conditions: Relapsed or Refractory Large B-cell Lymphoma

Summary: the purpose of this clinical trial is to learn if the study treatment loncastuximab tesirine and rituximab is safe and efficient before standard of care chimeric antigen receptor t-cell (car-t) therapy in patients with relapsed or refractory large b-cell lymphoma.


Eligibility criteria:
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. 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 exclusion criteria: * previous treatment with any anti-cd19 therapy including lonca or prior cd19 car t-cell therapy * subjects receiving investigational car-t products * major surgery within 4 weeks prior to starting study therapy. * history of bleeding diathesis (e.g., von willebrand's disease), hemophilia, or active bleeding. * subjects with chronic liver disease with hepatic impairment child-pugh class c * pregnant or lactating or intending to become pregnant during the study * active graft-versus-host disease * post-transplantation lymphoproliferative disorders * active autoimmune disease which, in the opinion of the investigator, may negatively impact subject safety or interfere with study participation. * the diagnosis of another malignancy which, in the opinion of the investigator, is likely to negatively impact subject safety or interfere with study participation. * subjects with known cns involvement. * significant medical diseases or conditions including those requiring substantial changes in concomitant medications, as assessed by the investigator, that would substantially increase the risk-to-benefit ratio of participating in the study. this includes, but is not limited to the following conditions: * cardiovascular disorders: * congestive heart failure new york heart association class iii or iv, unstable angina pectoris, serious cardiac arrhythmias. * myocardial infarction (mi) within 6 months before the first dose. * qtc prolongation defined as a qtcf \> 480 ms. * congenital long qt syndrome or a corrected qt measure (qtc) interval of \>480 ms at screening (unless secondary to pacemaker or bundle branch block). * severe pulmonary disease * uncontrolled diabetes mellitus * severely immunocompromised state * any other condition that would, in the investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns or compliance with clinical study procedures. * active systemic bacterial, viral, fungal, or other infection requiring systemic treatment at time of screening * hiv infection. * subjects with evidence of active hepatitis b infection, based on positive surface antigen or hepatitis b dna pcr are excluded. subjects who are hepatitis b core antibody positive must take prophylaxis with entecavir or equivalent and be willing to undergo monthly hepatitis b dna pcr testing. subjects with active hep c patients may be enrolled if other parameters precluding hepatic impairment are met and they are not undergoing active therapy for hepatitis c. * known prior severe hypersensitivity to a cd19 antibody, lonca (including sg3249) or any of its excipients, or history of positive serum human ada to a cd19 antibody. * subjects taking prohibited medications as described in section 6.8.1. a washout period of prohibited medications for a period of at least five half-lives or as clinically indicated should occur before the start of treatment.