Recurrent or refractory B-cell lymphoma
Conditions
Interventions
Dose escalation phase - low dose group:Infuse 100 × 10^6 CAR-T cells per person
Dose escalation phase - medium dose group:Infuse 200 × 10^6 CAR-T cells per person
Dose escalation phase - high dose group:Infuse 300 × 10^6 CAR-T cells per person
Dose expansion phase:The safe and effective dose of C2302V1 cells determined during the dose escalation phase
Sponsors
The First People’s Hospital of Jingzhou
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1.Patients who meet the following diagnostic and treatment criteria for refractory/recurrent B-cell lymphoma (meeting one of the first four criteria plus the fifth): (1) After four courses of standard regimen chemotherapy, tumor reduction is less than 50% or there is disease progression; (2) Achieved CR after standard regimen chemotherapy but relapsed within 6 months; (3) Recurred two or more times after CR; (4) Not suitable for hematopoietic stem cell transplantation, or abandoned hematopoietic stem cell transplantation due to limitations, or relapsed after hematopoietic stem cell transplantation; (5) The subject must have received adequate prior treatment, including: 1) Anti-CD20 monoclonal antibody; 2) Combination chemotherapy with anthracyclines; 2.Age 18 to 75 years old, no gender restriction; 3.For lesion measurement during screening: intra-nodal lesions must have a long diameter of at least 1.5 cm, and extra-nodal lesions must have a long diameter greater than 1.0 cm (refer to Appendix I: Revised Lymphoma Response Evaluation Criteria (2014)); 4.Screening requires adequate bone marrow reserve, defined as meeting all of the following criteria: 1) Absolute Neutrophil Count (ANC) > 1.0×10^9/L; 2) Absolute Lymphocyte Count (ALC) >= 0.3×10^9/L; 3) Platelet (PLT) count >= 50×10^9/L. 5.Important organ functions are basically normal: 1) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =60 mL/min (Cockcroft and Gault formula); 4) Have minimum levels of pulmonary reserve, defined as 91% in non-oxygen dependent state; 5) International Normalized Ratio (INR) <=1.5 times ULN, and activated partial thromboplastin time (APTT) <=1.5 times ULN. 6.When screening, possess the vascular conditions for single nucleus cell collection; 7.Estimated survival period is more than 3 months; 8.ECOG score 0~2; 9.For women of childbearing age, the blood/urine pregnancy test must be negative within 3 days before the PRG2302 apheresis and cell infusion. Any male or female patient with reproductive potential must agree to use effective contraception throughout the study and for at least 1 year after the study treatment administration. According to the investigator's judgment, having reproductive potential means: biologically capable of having children and having normal sexual activity. Female patients who are not of reproductive potential (i.e., meet at least one of the following criteria): 1) undergone hysterectomy or bilateral oophorectomy, or 2) medically confirmed ovarian failure, or 3) medically confirmed postmenopausal (at least 12 consecutive months of amenorrhea). 10.Willing to sign the informed consent form.
Exclusion criteria
Exclusion criteria: 1.Patients with active primary or secondary central nervous system (CNS) lymphoma (patients with CNS disease symptoms must undergo lumbar puncture to rule out CNS lymphoma); 2.Exclude individuals with a history of central nervous system disorders, such as epilepsy, cerebral vascular ischemia/hemorrhage, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar diseases, organic brain syndrome, mental illnesses, or any autoimmune diseases involving the central nervous system; 3.Subjects with other malignancies within 5 years (excluding those who have been cured and have had no active disease for at least 3 years prior to screening, and excluding non-melanoma skin cancer, basal cell or squamous cell skin cancer, localized prostate cancer, ductal carcinoma in situ, papillary or follicular thyroid cancer, and carcinoma in situ); 4.Known to have active systemic autoimmune diseases and are currently undergoing treatment before screening; 5.For screening, any of the following conditions apply: 1) Hepatitis B surface antigen (HBsAg) and/or hepatitis B e antigen (HBeAg) positive; 2) Hepatitis B e antibody (HBe-Ab) and/or hepatitis B core antibody (HBc-Ab) positive, with HBV-DNA copy number greater than the measurable lower limit; 3) Hepatitis C antibody (HCV-Ab) positive; 4) Treponema pallidum antibody TP-Ab and TRUST both positive; 5) HIV antibody test positive; 6.There is uncontrollable active infection; 7.During screening, the heart must meet any of the following conditions: (1) Left Ventricular Ejection Fraction (LVEF) =140 mmHg and/or Diastolic Blood Pressure >=90 mmHg) or Pulmonary Hypertension; (4) History of Myocardial Infarction or cardiac surgery within 12 months prior to cell infusion; (5) Clinically significant valvular heart disease; 8.When screening, those with lymphoma involving the atrium or ventricle; 9.Those with acute clinical emergencies requiring urgent intervention due to obstruction or compression by lymphoma masses (such as intestinal obstruction or vascular compression); 10.Exclude those with active bleeding during screening; 11.Screen for those with a history of deep vein thrombosis or pulmonary embolism within the past 6 months; 12.Individuals who have used any of the following medications or treatments within the specified time before leukapheresis: 1) Alemtuzumab within 6 months before leukapheresis; 2) Cladribine within 3 months before leukapheresis; 3) Lymphocyte-toxic chemotherapy within 2 weeks before leukapheresis; exceptions for those who have exceeded 3 half-lives; 4) Anti-CD20 monoclonal antibodies within 3 months before leukapheresis; 5) Non-lymphocyte-toxic cytotoxic chemotherapy within 7 days before leukapheresis; exceptions for those who have exceeded 3 half-lives; 6) BCL-2 inhibitors (e.g., Venetoclax) within 4 days before leukapheresis; 7) PI3Kd kinase inhibitors (e.g., Idelalisib) within 2 days before leukapheresis; 8) Lenalidomide within 1 day before leukapheresis; 9) Radiation therapy within 6 weeks before leukapheresis; exceptions for those with PD during or after radiation therapy. 13.Patients who have received chemotherapy within 2 weeks prior to cell infusion, except for the following: 1) conditioning chemotherapy as per protocol; 2) intrathecal chemotherapy for
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety evaluation;Effectiveness evaluation; | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic evaluation;Pharmacodynamic evaluation;Pharmacodynamic evaluation;Pharmacodynamic evaluation;Pharmacodynamic evaluation; | — |
Countries
China
Contacts
Public ContactTan Jie
The First People’s Hospital of Jingzhou
Outcome results
None listed