clinical study of targeting cd19 and cd22 chimeric antigen receptor t lymphocytes in the treatment of recurrent or refractory b cell non-hodgkin lymphoma

Conditions: Relapsed and Refractory; Lymphoid Hematological Malignancies

Summary: clinical study of targeting cd19 and cd22 chimeric antigen receptor t lymphocytes in the treatment of recurrent or refractory b cell non-hodgkin lymphoma

this is a single-arm, single-center, open clinical study to evaluate the safety and efficacy of gc022f injection in patients with relapsed or refractory b-cell non-hodgkin's lymphoma.

Eligibility criteria:
inclusion criteria: 1. male or female, 18-75 years old (including the threshold value); 2. histologically confirmed as diffuse large b-cell lymphoma (dlbcl), transformed follicular lymphoma (tfl), or primary mediastinal b-cell lymphoma (pmbcl) : i. refractory b-nhl: pd was the optimal response to standard first-line treatment (those with intolerance to first-line treatment were not included in this study); or sd after at least 4 courses of first-line treatment, and the duration of sd shall not exceed 6 months after the last treatment; or the subjects' best response to the last treatment of second-line or above treatment is pd, or sd after at least 2 courses of second-line or above treatment, and the sd maintenance time is not more than 6 months; or: ii. relapsed b-nhl: after standard systemic treatment and complete remission after second-line treatment, the disease recurred as certified by histopathology, or the recurrence as confirmed by histopathology within 1 year after autologous hematopoietic stem cell transplantation (not limited by previous treatment methods); iii. patients with invert follicular lymphoma must receive chemotherapy prior to transformation and meet the above definition of recurrent or refractory after transformation; 3. according to lugano treatment response standard (2014 version), there should be at least one evaluable tumor lesion: the longest diameter of the injunctional lesion was \> 1.5cm, and the longest diameter of the injunctional lesion was b\> 1.0cm; 4. positive expression of cd19 and cd22 in biopsy sections of tumor tissues; 5. patients who have failed or relapsed after single-target car-t therapy may also be enrolled. 6. prior to the study, the approved anti-b-nhl treatment, such as systemic chemotherapy, general radiotherapy and immunotherapy, has been completed for at least 2 weeks; 7. ecog≤1； 8. expected survival ≥3 months; 9. absolute count of neutrophils ≥ 1×109/l; 10. platelet count ≥50×109/l; 11. absolute lymphocyte count ≥1×108/l; 12. adequate organ function reserve: 1. alanine aminotransferase and aspartate aminotransferase ≤ 2.5× unl (upper limit of normal value); 2. creatinine clearance rate (cockcroft-gault method) ≥60 ml/min; 3. serum total bilirubin ≤1.5× unl; 4. the left ventricular ejection fraction (lvef) of the subject was diagnosed by echocardiography ≥50%, and no clinically significant pericardial effusion was observed, and no clinically significant ecg abnormalities were observed; 5. under natural indoor air environment, the basic oxygen saturation of \> is 92%; 13. vein access required for collection can be established, and there are no contraindications for leukocyte collection; 14. women of childbearing age had negative pregnancy test during screening period and before administration, and agreed to take effective contraceptive measures at least one year after infusion; male subjects with fertile partners must agree to use effective barrier contraceptive method at least one year after infusion and avoid sperm donation; 15. voluntary signing of informed consent. exclusion criteria: 1. other tumors (except cured non melanoma skin cancer, cervical cancer in situ, superficial bladder cancer, breast ductal carcinoma in situ, or other malignant tumors with complete remission for more than 5 years); 2. persons with severe mental disorders; 3. a history of hereditary diseases such as fanconi anemia, schrader syndrome, costerman syndrome, or any other known bone marrow failure syndrome; 4. a history of allogeneic stem cell transplantation; 5. heart disease with grade iii-iv heart failure \[new york heart association (nyha) classification\] or myocardial infarction, cardiac angioplasty or stenting, unstable angina pectoris, or other clinically significant cardiac conditions within the year prior to enrollment; 6. the presence of any indwelling catheter or drainage tube (e.g., percutaneous nephrostomy tube, bile drainage tube or pleural/peritoneal/pericardial catheter), allowing the use of a dedicated central venous catheter; 7. subjects with a history of cns lymphoma, cerebrospinal fluid malignant cells or brain metastasis; 8. a history or disease of the central nervous system, such as seizure disorder, cerebral ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease involving cns; 9. the results of any of the following virology-elisa tests were positive: hiv antibody, hcv antibody, tppa, hepatitis b surface antigen; 10. there were active infections requiring systematic treatment within 2 weeks before single collection; 11. persons with a known severe allergic reaction to cyclophosphamide or fludarabine, or with an allergic constitution; 12. a history of an autoimmune disease (e.g., crohn's disease, rheumatoid arthritis, systemic lupus erythematosus) that has caused injury to the terminal organs or requires systemic immunosuppressive/disease-modulating drugs within the past 2 years; 13. pulmonary fibrosis is present; 14. has received treatment in another clinical trial within 4 weeks prior to participation in this trial, or the date of signing of the informed consent is within 5 half-lives (whichever is longer) of the last medication used in the last other clinical trial; 15. poor compliance due to physiological, family, social, geographical and other factors, unable to comply with the research program and follow-up plan; 16. the presence of a comorbiditie requiring systemic corticosteroid therapy (≥5 mg/ day of prednisone or equivalent dose of other corticosteroids) or other immunosuppressive agents within 6 months of study treatment was determined by the investigator; 17. lactating women who do not want to stop breastfeeding; 18. any other condition that the researcher considers inappropriate to be included in the study.

Keywords: lymphoid hematological malignancies car-t cell therapy cd19 cd22