CD19-positive relapsed or refractory acute B lymphocytic leukemia
Conditions
Interventions
Group 1:1.5x10^4CAR+T cells/kg
Group 2:3.0x10^4CAR+T cells/kg
Sponsors
Peking University Third Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. Aged 18-70 years (including critical value), gender is not limited; 2. ECOG score = 12 weeks; 4. Positive expression of CD19 in tumor cells detected by bone marrow or peripheral blood flow; 5. The bone marrow examination is clearly diagnosed as acute B lymphocytic leukemia and one of the following conditions is met: (1) Refractory B-ALL: Those who have not achieved complete remission after 2 courses of standard induction chemotherapy, or those who have not achieved complete remission after first-line/multi-line salvage chemotherapy; (2) Recurrent B-ALL: relapse within 12 months after the first remission, or relapse after first-line/multi-line salvage chemotherapy; (3) Relapse after autologous or allogeneic hematopoietic stem cell transplantation; In addition, subjects with Philadelphia chromosome positive (Ph+) should have received at least 2 tyrosine kinase inhibitors (TKI) treatment failure, or can not tolerate TKI treatment, or accompanied by t315i mutation, resistant to TKI drugs ; 6. Morphological examination of bone marrow cells showed that the proportion of primitive and immature lymphocytes in the bone marrow was more than 5%; 7. Have not received hematopoietic stem cell transplantation within 6 months before enrollment; 8. Good organ function reserve: (1) Creatinine clearance rate (Cockcroft-Gault method) > 60 mL/min: male creatinine clearance rate = [(140-age) x body weight (kg)]/[0.818 x creatinine (umol/L)]; female creatinine clearance rate = [(140-age) x body weight (kg) x 0.85]/[0.818 x creatinine (umol/L)]; (2) Serum ALT and AST= 0.1x10^9/L; (5) The left ventricular ejection fraction (LVEF) of the subjects was diagnosed by echocardiography >50%, and the echocardiography showed no clinically significant pericardial effusion; (6) No clinically significant pleural effusion; (7) Under the indoor air environment, the oxygen saturation at the end of the base finger is more than 92%; 9. Female subjects of childbearing age must be in non-breastfeeding period, and the high-sensitivity serum pregnancy test or urine pregnancy test must be negative during the screening period of fertile females, all subjects must use medically approved contraceptive measures (such as intrauterine devices, contraceptives) throughout the treatment period and within 2 years after cell reinfusion, and male subjects should also avoid sperm donation; 10. The required venous access can be established, and the collection of peripheral blood mononuclear cells can be performed according to the judgment of the investigator; 11. Voluntarily sign the informed consent; 12. The subjects can communicate well with the investigator, are willing and able to follow the trial plan, and complete the trial in accordance with the trial regulations.
Exclusion criteria
Exclusion criteria: 1. Simple extramedullary leukemia or simple extramedullary relapse; 2. Leukemia central nervous system involving CNS3; 3. Suffering from other malignant tumors, except the following: cured non-melanoma skin cancer, cervical cancer in situ, localized prostate cancer, superficial bladder cancer, ductal carcinoma in situ, or other malignant tumors with a disease-free survival of more than 5 years; 4. The test result of any of the following infectious diseases is positive: HIV; HCV; HBsAg; HBcAb positive, and HBV DNA copy number is detected at the same time; TPPA; 5. Have been vaccinated with live vaccine within 4 weeks before enrollment; 6. Ph+ ALL who have received TKI treatment within 1 week before enrollment; 7. Previously received CD19 targeted therapy or CAR-T therapy or other gene editing T cell therapy; 8. Acute graft versus host disease (GVHD) (Glucksberg criteria) or extensive chronic GVHD (Seattle criteria) requiring treatment of grade >=2 within 4 weeks before enrollment, or those who may need to receive anti-GVHD therapy during the trial period as judged by the investigator; 9. According to the investigator's judgment, there are comorbidities that need to be treated with systemic corticosteroids or other immunosuppressive drugs during the trial; or have received allogeneic cell therapy within 4 weeks before enrollment, such as donor lymphocyte infusion (DLI); 10. Received CNS-directed radiotherapy within 4 weeks before enrollment; 11. Acute toxic and side effects caused by previous treatment have not recovered to grade 1 or below (except for hematological toxicity and alopecia); 12. Known life-threatening hypersensitivity reactions or other intolerances to cyclophosphamide or fludarabine or severe allergic conditions; 13. Active autoimmune diseases (including but not limited to systemic lupus erythematosus, Sjogren's syndrome, rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory bowel disease, Hashimoto's thyroiditis, etc., except for hypothyroidism controllable by hormone replacement therapy alone); 14. Have received major surgery requiring general anesthesia within 4 weeks before enrollment, or have not recovered from previous surgical treatment and achieved clinical stability, or are expected to require major surgery under general anesthesia during the trial; 15. Have used other clinical trial drugs within 28 days before enrollment; 16. Suffering from any unstable circulatory system disease within 6 months before enrollment, including but not limited to unstable angina pectoris, myocardial infarction, heart failure [New York Heart Association (NYHA) classification >= grade III], serious arrhythmia requiring drug treatment, or cardiac angioplasty or coronary stenting or heart bypass surgery within 6 months prior to enrollment; 17. There is a history or disease of the central nervous system, such as seizure disorder, cerebrovascular ischemia/bleeding, dementia, cerebellar disease, or any autoimmune disease involving the CNS; 18. Uncontrollable active infection (such as sepsis, bacteremia, fungemia, viremia) at the time of screening; 19. The investigator believes that it is not suitable to participate in this clinical trial due to any other circumstances.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose limiting toxicity;Adverse event; | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall response rate;Percentage of subjects achieving CR or CRi and negative for minimal residual disease (MRD);Proportion of subjects assessed for CR or CRi;Duration of remission (DOR);Progression-free survival (PFS);Overall survival (OS);Incidence of GC019F antibody in peripheral blood;Levels of cytokines in peripheral blood and cerebrospinal fluid (if applicable) that may be associated with cytokine response and neurotoxicity; | — |
Countries
China
Contacts
Public ContactWang Zhen'guang
Gracell Biotechnology (Shanghai) Co., LTD.
Outcome results
None listed