a combination study of car-t therapy in r/r b-nhl

Conditions: Diffuse Large B Cell Lymphoma

Summary: in registry studies of car-t products that have been marketed globally, patients with relapsed or refractory b-cell non-hodgkin's lymphoma (r/r b-nhl) have been enrolled to receive car-t infusion in combination with tyrosine kinase inhibitors (btki) or immune checkpoint inhibitors (pd-1 or pd-l1 antibodies), with objective remission rate (orr) for car-t in combination with btki ranging from 83.3%-100% and complete remission rate (crr) were 33.3-75%. the orrs for objective remission rates for car-t combined with pd1/pd-l1 ranged from 50-91% and crrs were 33.3-64%, respectively. with regard to safety, no dose-limiting toxic (dlt) occurred and the incidence of other adverse reactions was low, and studies demonstrated that btki or pd-1/pd-l1 antibodies could further enhance the responsiveness and durability of anti-cd19 car-t cell therapy. however, there are no studies exploring the efficacy and safety of clinical regimens using btki + radiotherapy ± chemotherapy as a bridging regimen to treat r/r b-nhl in combination with btki and/or pd-1 inhibitor after car-t cell infusion. in real-world applications of commercial car-t, car-t therapy combined with btki or pd-1/pd-l1 antibodies may further improve response rates and remission persistence in r/r b-nhl patients receiving car-t infusion back, with efficacy benefits while ensuring a manageable safety profile. therefore, our center plans to conduct a phase ii clinical study of regent car-t 001(a phase ii study of btki+radiotherapy±chemotherapy bridging before car-t cell therpay in combination with btki±pd-1 inhibitor for r/r b-nhl).


Eligibility criteria:
inclusion criteria: * histologically confirmed diagnosis of b-cell non-hodgkin's lymphoma; and according to the 2014 lugano diagnostic criteria. * patients who have relapsed or are refractory to at least prior first-line therapy, including anthracycline-containing chemotherapy regimens and anti-cd20 monoclonal antibody therapy; patients must meet the definitions of refractory and relapsed. * no prior cd19 car-t cell therapy * adequate organ function to receive car-t cell therapy * vascular condition adequate to perform leukapheresis * able to provide written informed consent (icf) and able to understand and agree to comply with the study requirements and assessment schedule * patients of childbearing potential must be willing to use highly effective contraception for the duration of the study, and for 120 days after the last dose of treatment. * ecog 0-2 exclusion criteria: * history of allogeneic hematopoietic stem cell transplantation; * history of epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease or any autoimmune disease involving the central nervous system; * presence or current concurrent other malignancies within the past 2 years, with the exception of cured cervical carcinoma in situ, non-melanoma skin cancer and superficial bladder tumors (ta (non-invasive tumors), tis (carcinoma in situ) and t1 (tumor infiltrating basement membrane)); * serious cardiovascular disease: grade ii or higher myocardial ischemia or myocardial infarction, poorly controlled arrhythmias; grade iii-iv cardiac insufficiency by nyha criteria, or cardiac ultrasound suggestive of left ventricular ejection fraction (lvef) \<50%; * hypersensitivity to any study drug or excipient; * patients with active viral hepatitis requiring treatment as determined by the investigator: chronic hepatitis b virus carriers with hbv dna ≥ 500 iu/ml (2500 copies/ml) (hbv dna testing only for patients who test positive for hepatitis b surface antigen or core antibody); patients who test positive for hcv rna (hcv testing only for patients who test positive for hepatitis c virus antibody) rna testing); * patients with any active autoimmune disease (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enterocolitis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism), or a known history of allogeneic organ transplantation, or long-term heavy use of hormones or use of other immunomodulatory agents, or other patients assessed by the investigator as having implications for study treatment ; * the presence of an active infection; * history of uncontrollable systemic disease, including diabetes, hypertension, acute lung disease, etc; * known human immunodeficiency virus (hiv) infection; * presence of an underlying medical condition or alcohol/drug abuse or dependence that is detrimental to study drug administration, or that may affect interpretation of results, or that places the patient at high risk of developing treatment complications; * organ damage due to an autoimmune disease (e.g., crohn's disease, rheumatoid arthritis, systemic lupus erythematosus) or the need for systemic application of immunosuppressive or other systemic disease-controlling drugs within the past 2 years.