a phaseⅰb study evaluating safety and efficacy of c-car011 treatment in b- nhl subjects

Conditions: B-cell Non-Hodgkin Lymphoma

Summary: this is a single arm, single-center, non-randomized study to evaluate the safety and efficacy of c-car011 therapy in relapsed or refractory b cell non-hodgkin lymphoma (nhl).

the study will include the following sequential phases: screening, pre- treatment (cell product preparation; lymphodepleting chemotherapy), treatment and follow-up

Eligibility criteria:
inclusion criteria: * volunteered to participate in this study and signed informed consent. * age 18-70 years old, male or female. * relapse or refractory b cell non-hodgkin's lymphoma ,histologically diagnosed as dlbcl,follicular lymphoma and mantle cell lymphoma according to the nccn. nonhodgkin's lymphoma clinical practice guidelines (2017 version 1) 1. dlbcl and follicular lymphoma (stage ⅲ-ⅳ, grade ⅲb). 1. progressive disease after the last standard chemotherapy regimens. 2. stable disease after the last standard chemotherapy regimens(at least 4 cycles of first-line therapy or 2 cycles of later-line therapy). 3. relapse or progressive disease within 12 months after autologous stem cell transplantation (sct). 2. follicular lymphoma (stage ⅲ-ⅳ) (gradeⅰ-ⅲa) 1. relapse or progressive disease within 1 year after the last standard chemotherapy regimens(at least 2 combination chemotherapy regimens). 2. stable disease after the last standard chemotherapy regimens(at least 2 cycles of combination chemotherapy regimens). 3. mantle cell lymphoma 1. relapse after 1st cr or persistent disease, and not eligible or appropriate for sct. 2. relapse or progressive disease within 1 year after the last chemotherapy regimens(at least 4 cycles of first-line therapy or 2 cycles of later- line therapy). 3. relapse or progressive disease within 12 months after autologous sct. * all subjects must have received anti-cd20 monoclonal antibody (unless tumor is cd20-negative) and anthracycline-containing chemotherapy regimens according to nccn non-hodgkin lymphoma clinical practice guidelines (2017 version 1). * at least one measurable lesion per revised iwg response criteria (the longest diameter of the tumor ≥ 1.5cm). * expected survival ≥ 12 weeks. * ecog score 0-1. * left ventricular ejection fraction (lvef) ≥ 50% (detected by echocardiography). * no active pulmonary infections, normal pulmonary function and oxygen saturation ≥ 92% on room air. * at least 2 weeks from receiving previous treatment (radiotherapy or chemotherapy) prior to leukapheresis. * no contraindications of leukapheresis. * female subjects in childbearing age, their serum or urine pregnancy test must be negative, and must agree to take effective contraceptive measures during the trial. exclusion criteria: * history of allergy to cellular products. * laboratory tests: absolute neutrophil count \ 1.5 uln, serum creatinine \> uln, alt/ast \> 3 uln. * history of car t cell therapy or any other genetically modified t cell therapy. * relapse after allogeneic hematopoietic stem cell transplantation. * active infections that require treatment (uncomplicated urinary tract infections and bacterial pharyngitis are allowed), prophylactic antibiotic, antiviral and antifungal treatment are permitted. * hepatitis b or hepatitis c virus infection (including carriers), syphilis, as well as acquired or congenital immune deficiency diseases, including but not limited to hiv infection. * class iii or iv heart failure according to the nyha heart failure classifications. * qt interval prolongation ≥ 450 ms. * history of epilepsy or other central nervous system disorders. * evidence of cns lymphoma by head enhancement scan or magnetic resonance imaging. * history of other primary cancers, with the following exceptions. 1. excisional non-melanoma (e.g. cutaneous basal cell carcinoma). 2. cured in situ carcinoma (e.g. cervical cancer, bladder cancer, breast cancer). * autoimmune diseases that require treatment, immune deficiency diseases or other diseases that require immunosuppressive therapy. * used of systemic steroids within two weeks (using inhaled steroids is an exception). * women who are pregnant or lactating, or who have breeding intent in 6 months. * participated in any other clinical trial within three months. * any situation that investigators believe the risk of the subjects is increased or results of the trial are disturbed.

Keywords: b-cell non-hodgkin lymphoma refractory relapsed