Donor Derived CD19 CAR-T Cells in the Treatment of R/R B-cell Acute Lymphoblastic Leukemia

Official title

A Clinical Study on the Safety and Effectiveness of Donor Derived CD19 CAR-T Cells in the Treatment of R/R B-cell Acute Lymphoblastic Leukemia

Overview

A Clinical Study on the Safety and Effectiveness of donor derived CD19 CAR-T Cells in the treatment of R/R B-cell acute lymphoblastic leukemia

Detailed description

In this study, 15 patients with relapsed refractory B-cell acute lymphoblastic leukemia were proposed to undergo CD19 CAR-T Cells therapy. Under the premise that its safety has been clarified in previous studies, further observation and evaluation of the effectiveness of CD19 CAR-T Cells therapy for relapsed refractory B-cell acute lymphoblastic leukemia; At the same time, on the basis of expanding the sample size, more safety data on CD19 CAR-T Cells treatment for relapsed refractory B-cell acute lymphoblastic leukemia were accumulated.

Interventions

• Biological CD19 B-cell Acute Lymphoblastic Leukemia Targeted CAR T-cells injection
  Each subject receive CD19 B-cell Acute Lymphoblastic Leukemia Targeted CAR T-cells by intravenous infusion

Primary outcome measures

• Dose-limiting toxicity (DLT) [Time frame: Up to 28 days after Treatment]
• Incidence of treatment-emergent adverse events (TEAEs) [Time frame: Up to 2 years after Treatment]

Secondary outcome measures (3)

• Duration of remission ,DOR [Time frame: Up to 1 years after CAR-T infusion]
• Overall survival, OS [Time frame: Up to 2 years after Treatment]
• Event-free survival (EFS) [Time frame: Up to 1 years after CAR-T infusion]

Eligibility criteria

Inclusion criteria

• 1\. Age ≥18 years old, gender unlimited;
• 2\. Abnormal B cell immunotyping was CD19 positive;
• 3\. Patients diagnosed with B-cell acute lymphoblastic leukemia by histological or immunotyping;
• 4\. Meets the diagnosis of relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) and includes any of the following conditions:

• No CR was obtained after standard chemotherapy;
• CR was induced for the first time, but the duration of CR was less than 12 months;
• R/R B-ALL that does not work after the first or more remedial treatments;
• Two or more relapses;
• 5\. The researchers believed that the patient had been adequately treated, such as auto-HSCT, auto-CART could not be prepared or preparation failed. Autologous CAR-T preparation failure was defined as including too few autologous lymphocytes (<1×109) or insufficient expansion during preparation or failure to meet the release criteria;
• 6\. Total bilirubin ≤51 ( μmol/L), alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 3 times the upper limit of normal, creatinine ≤176.8 (μmol/L);
• 7\. Absolute neutrophil count: ≥ 0.5×109/L; Platelet: ≥ 30×109/L; Hemoglobin ≧60g/L;
• 8\. Echocardiography showed left ventricular ejection fraction (LVEF) ≥40%;
• 9\. The estimated survival is more than 3 months;
• 10\. ECOG score 0-2;
• 11\. Women and men who are fertile must consent to the use of appropriate contraception before entering the study, during study participation, and for 6 months after transfusion (the safety of this therapy for the unborn child is not known, with unknown risks);
• 12\. Subjects who are willing to participate in the study are able to understand and have the ability to sign informed consent.

Exclusion criteria

• 1\. Known allergies to research preconditioning measures, etc;
• 2\. People with a history of epilepsy or other central nervous system disorders;
• 3\. People with a history of prolonged QT or severe heart disease;
• 4\. Less than 100 days after receiving allogeneic hematopoietic stem cell transplantation;
• 5\. Hiv-infected person;
• 6\. Persons with active hepatitis B or C virus; Those who are not cured have active infections;
• 7\. Insufficient amplification ability (< 5x) in response to CD3 / CD28 costimulatory signals;
• 8\. Combined use of systemic steroids (e.g., prednisone ≥20mg) within 3 days prior to screening, except for ongoing or intermittent use of topical, inhaled or intranasal steroids within 2 weeks or at present; Or have systemic diseases that require long-term use of immunological agents;
• 9\. Patients who received anti-cancer chemotherapy or other drugs within 2 weeks prior to screening;
• 10\. Any situation that the investigator believes may increase the risk of the subjects or interfere with the study results.

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

China · 1 center

• The first affiliated hospital of medical college of zhejiang university — Hangzhou

Identifiers

NCT: NCT06793241 · TXB2024011

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗