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 Details
Study Description
Brief 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
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1/Phase 2 |
Detailed Description
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Administration of GC022F CAR-T cells Each subject receive GC022F CAR T-cells by intravenous infusion |
Drug: GC022F CAR-T cells
Each subject receive GC022F CAR-T cells by intravenous infusion
Other Names:
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Outcome Measures
Primary Outcome Measures
- Dose-limiting toxicity (DLT) [Within 28 days after cell infusion]
Proportion of patients with dose limiting toxicity (DLT) after cell infusion
- Incidence of treatment-emergent adverse events (TEAEs) [24 months after cell infusion]
Incidence of treatment-emergent adverse events [Safety and Tolerability]
Secondary Outcome Measures
- Overall response rate(ORR) [Month 1,3,6,12,18and 24]
Assessment of ORR (ORR = CR + CRi ) at Month 1,3,6,12,18and 24
- Progression-free survival (PFS) [Month 6,12,18and 24]
Assessment of PFS at Month 6,12,18and 24
- Overall survival (OS) [Month 6,12,18and 24]
Assessment of OS at Month 6,12,18and 24
- Duration of response(DOR) [Month 6,12,18and 24]
Assessment of OS at Month 6,12,18and 24
Eligibility Criteria
Criteria
Inclusion Criteria:
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Male or female, 18-75 years old (including the threshold value);
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Histologically confirmed as diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (TFL), or primary mediastinal B-cell lymphoma (PMBCL) :
- 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:
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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);
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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;
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Positive expression of CD19 and CD22 in biopsy sections of tumor tissues;
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Patients who have failed or relapsed after single-target CAR-T therapy may also be enrolled.
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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;
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ECOG≤1;
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Expected survival ≥3 months;
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Absolute count of neutrophils ≥ 1×109/L;
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Platelet count ≥50×109/L;
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Absolute lymphocyte count ≥1×108/L;
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Adequate organ function reserve:
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ALANINE aminotransferase and aspartate aminotransferase ≤ 2.5× UNL (upper limit of normal value);
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Creatinine clearance rate (Cockcroft-Gault method) ≥60 mL/min;
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Serum total bilirubin ≤1.5× UNL;
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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;
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under natural indoor air environment, the basic oxygen saturation of > is 92%;
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Vein access required for collection can be established, and there are no contraindications for leukocyte collection;
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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;
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Voluntary signing of informed consent.
Exclusion Criteria:
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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);
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Persons with severe mental disorders;
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A history of hereditary diseases such as Fanconi anemia, Schrader syndrome, Costerman syndrome, or any other known bone marrow failure syndrome;
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A history of allogeneic stem cell transplantation;
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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;
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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;
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Subjects with a history of CNS lymphoma, cerebrospinal fluid malignant cells or brain metastasis;
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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;
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The results of any of the following virology-ELISA tests were positive: HIV antibody, HCV antibody, TPPA, hepatitis B surface antigen;
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There were active infections requiring systematic treatment within 2 weeks before single collection;
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Persons with a known severe allergic reaction to cyclophosphamide or fludarabine, or with an allergic constitution;
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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;
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Pulmonary fibrosis is present;
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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;
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Poor compliance due to physiological, family, social, geographical and other factors, unable to comply with the research program and follow-up plan;
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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;
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Lactating women who do not want to stop breastfeeding;
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Any other condition that the researcher considers inappropriate to be included in the study.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | The first affiliated hospital of medical college of zhejiang university | Hangzhou | Zhejiang | China | 310003 |
Sponsors and Collaborators
- He Huang
- Gracell Biotechnology Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GC022F-ZhejiangU