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

Overview

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

• Biological humanized 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

Primary outcome measures

• ORR [Time frame: 3 years]

Eligibility criteria

Inclusion criteria

• Newly treated patients with acute B-lymphocytic leukaemia/lymphoma who are clinically determined to be unable to tolerate strong chemotherapy;
• age 18-80 years old (including boundary value), both men and women can;
• The physical status of the American Eastern Cancer Collaboration Group (ECOG) was 0\~2 points;
• Positive CD19 confirmed by flow cytometry and/or histopathology;
• The expected survival period from the date of signing the informed consent form is more than 3 months.；
• 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；
• 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

• severe cardiac insufficiency, left ventricular ejection fraction <50%;
• have a history of severe lung function impairment;
• Combined with other advanced malignant tumors;
• Had severe infection within 4 weeks before enrollment and could not be effectively controlled;
• suffering from serious autoimmune diseases or immune deficiency diseases;
• active hepatitis (HBV DNA quantitative > 500IU/ml\] or HCV ribose Nucleic acid \[HCVRNA\] test positive);
• human immunodeficiency virus (HIV) infection or known to have acquired immunodeficiency syndrome Co-syndrom (AIDS), or syphilis infection;
• Have a history of severe allergy to biological products (including antibiotics), antibodies or cytokines Allergy to macromolecular biological drugs;
• Acute graft-versus-host reactions were still present one month after immunosuppressant discontinuation Patients with allogeneic hematopoietic stem cell transplantation (GvHD);
• 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.);
• 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;
• Suffering from mental illness;
• The patient has substance abuse/addiction;
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07335094 · 2024LX0089_GY

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗