A Clinical Study of Humanized CD19 CAR-T Cells With TLR2 for the Treatment of Adult Patients With Naive B-Cell Acute Lymphoblastic Leukemia/Lymphoma Who Are Intolerant to Intensive Chemotherapy

Zhujiang Hospital

Status and phase: Begins enrollment in 3 months; Early Phase 1

Conditions: B Lymphoblastic Leukemia/Lymphoma

Treatments: Biological: humanized CD19 CAR-T Cells with TLR2

Study type: Interventional

Funder types: Other

Identifiers

NCT07335094

2024LX0089_GY

Details and patient eligibility

About

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.

Full 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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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60 participants in 1 patient group

Experimental Arm

Experimental group

Description:

Administer a single infusion of humanized CD19 CAR-T Cells with TLR2 to this group of patients following fludarabine plus cyclophosphamide (F+C) lymphodepletion, and conduct follow-up surveys at the required time points within three years post-infusion according to the visit schedule.

Treatment:

Biological: humanized CD19 CAR-T Cells with TLR2