B Lymphoblastic Leukemia/Lymphoma
Conditions
Keywords
CAR-T, CD19
Brief summary
The purpose of this clinical trial is to tolerability and safety of humanized CD19 CAR-T therapy with TLR2 in adult patients with acute B lymphoblastic leukemia/lymphoma who cannot tolerate intense chemotherapy at initial treatment. Participants will receive a single infusion of CD19 CAR-T and complete follow-ups over the next three years.
Detailed description
Objective: To evaluate the tolerability and safety of humanized CD19 CAR-T therapy with TLR2 in adult patients with acute B lymphoblastic leukemia/lymphoma who cannot tolerate intense chemotherapy at initial treatment. Secondary objective: To evaluate the efficacy and cytodynamics of humanized CD19 CAR-T therapy with TLR2 in adult acute B lymphoblastic leukemia/lymphoma who cannot tolerate intense chemotherapy at initial treatment.
Interventions
BIOLOGICALhumanized CD19 CAR-T Cells with TLR2
Administer a single infusion of humanized CD19 CAR-T Cells with TLR2 to this group of patients following fludarabine plus cyclophosphamide (F+C) lymphodepletion
Sponsors
Zhujiang Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Newly treated patients with acute B-lymphocytic leukaemia/lymphoma who are clinically determined to be unable to tolerate strong chemotherapy; 2. age 18-80 years old (including boundary value), both men and women can; 3. The physical status of the American Eastern Cancer Collaboration Group (ECOG) was 0\ 2 points; 4. Positive CD19 confirmed by flow cytometry and/or histopathology; 5. The expected survival period from the date of signing the informed consent form is more than 3 months.； 6. women of childbearing age screening period human chorionic gonadotropin (HCG) test negative, and Consent to use contraception for at least 1 year after the infusion; A man whose partner is fertile Subjects must agree to use an effective barrier contraceptive method for at least 1 year after the infusion； 7. the patient's main tissues and organs function well: (1) Liver function: ALT/AST\<3 times the upper limit of normal (ULN) and total bilirubin ≤34.2μmol/L; (2) Renal function: creatinine clearance (Cockcroft-Gault method) ≥60mL/min; (3) Lung function: blood oxygen saturation ≥95%, and no active lung infection; (4) Cardiac function: left ventricular ejection fraction (LVEF) ≥50%; No large number of pericardium was found Fluid accumulation, no clinically significant electrocardiogram abnormalities；
Exclusion criteria
1. severe cardiac insufficiency, left ventricular ejection fraction \<50%; 2. have a history of severe lung function impairment; 3. Combined with other advanced malignant tumors; 4. Had severe infection within 4 weeks before enrollment and could not be effectively controlled; 5. suffering from serious autoimmune diseases or immune deficiency diseases; 6. active hepatitis (HBV DNA quantitative \> 500IU/ml\] or HCV ribose Nucleic acid \[HCVRNA\] test positive); 7. human immunodeficiency virus (HIV) infection or known to have acquired immunodeficiency syndrome Co-syndrom (AIDS), or syphilis infection; 8. Have a history of severe allergy to biological products (including antibiotics), antibodies or cytokines Allergy to macromolecular biological drugs; 9. Acute graft-versus-host reactions were still present one month after immunosuppressant discontinuation Patients with allogeneic hematopoietic stem cell transplantation (GvHD); 10. in the pregnancy period (urine/blood pregnancy test positive) or breastfeeding women; nearly Men or women who plan to conceive within 1 year; Not guaranteed to be taken within 1 year after enrollment Effective contraception (condoms or contraceptives, etc.); 11. History of clinically significant central nervous system diseases, such as epilepsy, paresis, and loss Speech, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic Cerebral syndrome; 12. Suffering from mental illness; 13. The patient has substance abuse/addiction; 14. Use of banned drugs. (1). Hormones: within 7 days before leukocyte collection, or within 72 hours before CD19CAR-T administration A past therapeutic dose of corticosteroid (defined as prednisone or equivalent \> 20mg/day) Days). However, the use of physiological substitutes, topical and inhaled steroids is permitted. (2) Chemotherapy: rescue chemotherapy was received within 2 weeks before white blood cell collection. (3) Allogeneic cell therapy: donor lymphocytes were received within 4 weeks before white blood cell collection Infusion. (4).GVHD treatment: Anti-GVHD received within 4 weeks prior to CD19CAR T cell infusion Heal. (5) Alenzumab was used within 6 months before white blood cell collection, or chlorine was used within 3 months Farabine or cladobine.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ORR | 3 years | Objective response rates (ORR), including CR and PR, were analyzed by Clopper-Pearson distribution with bilateral 95% confidence intervals. For progression-free survival (PFS), Kaplan-Meier method was used to estimate the survival curve. Overall survival: the time from cell retransfusion until death from any cause. |
Contacts
Primary ContactYuhua LI, Ph.D.
Outcome results
None listed