Clinical Study of Targeting CD19 and CD22 Chimeric Antigen Receptor T Lymphocytes in the Treatment of Recurrent or Refractory B Cell Non-Hodgkin Lymphoma

Study Overview
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Brief Summary
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Clinical Study of Targeting CD19 and CD22 Chimeric Antigen Receptor T Lymphocytes in the Treatment of Recurrent or Refractory B Cell Non-Hodgkin Lymphoma

Detailed Description
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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.

Official Title
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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
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Relapsed and Refractory, Lymphoid Hematological Malignancies

Intervention / Treatment
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* Drug: GC022F CAR-T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 18-75 years old (including the threshold value); 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; 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; Positive expression of CD19 and CD22 in biopsy sections of tumor tissues; Patients who have failed or relapsed after single-target CAR-T therapy may also be enrolled. 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; ECOG≤1； Expected survival ≥3 months; Absolute count of neutrophils ≥ 1×109/L; Platelet count ≥50×109/L; Absolute lymphocyte count ≥1×108/L; Adequate organ function reserve: ALANINE aminotransferase and aspartate aminotransferase ≤ 2.5× UNL (upper limit of normal value); Creatinine clearance rate (Cockcroft-Gault method) ≥60 mL/min; Serum total bilirubin ≤1.5× UNL; 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; under natural indoor air environment, the basic oxygen saturation of > is 92%; Vein access required for collection can be established, and there are no contraindications for leukocyte collection; 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; Voluntary signing of informed consent. Exclusion Criteria: 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); Persons with severe mental disorders; A history of hereditary diseases such as Fanconi anemia, Schrader syndrome, Costerman syndrome, or any other known bone marrow failure syndrome; A history of allogeneic stem cell transplantation; 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; 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; Subjects with a history of CNS lymphoma, cerebrospinal fluid malignant cells or brain metastasis; 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; The results of any of the following virology-ELISA tests were positive: HIV antibody, HCV antibody, TPPA, hepatitis B surface antigen; There were active infections requiring systematic treatment within 2 weeks before single collection; Persons with a known severe allergic reaction to cyclophosphamide or fludarabine, or with an allergic constitution; 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; Pulmonary fibrosis is present; 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; Poor compliance due to physiological, family, social, geographical and other factors, unable to comply with the research program and follow-up plan; 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; Lactating women who do not want to stop breastfeeding; Any other condition that the researcher considers inappropriate to be included in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Administration of GC022F CAR-T cells<br>Each subject receive GC022F CAR T-cells by intravenous infusion | Drug: GC022F CAR-T cells<br>* Each subject receive GC022F CAR-T cells by intravenous infusion<br>* Other names: GC022F CAR-T cells injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity (DLT) | Proportion of patients with dose limiting toxicity (DLT) after cell infusion | Within 28 days after cell infusion | 
| Incidence of treatment-emergent adverse events (TEAEs) | Incidence of treatment-emergent adverse events [Safety and Tolerability] | 24 months after cell infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate(ORR) | Assessment of ORR (ORR = CR + CRi ) at Month 1,3,6,12,18and 24 | Month 1,3,6,12,18and 24 | 
| Progression-free survival (PFS) | Assessment of PFS at Month 6,12,18and 24 | Month 6,12,18and 24 | 
| Overall survival (OS) | Assessment of OS at Month 6,12,18and 24 | Month 6,12,18and 24 | 
| Duration of response(DOR) | Assessment of OS at Month 6,12,18and 24 | Month 6,12,18and 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lymphoid hematological malignancies, CAR-T cell therapy, CD19, CD22