Clinical trial NCT06793241: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: B-cell Acute Lymphoblastic Leukemia
Keywords: CD19 CAR-T
Lead sponsor: Zhejiang University
Sponsor class: OTHER
Collaborators: name: Yake Biotechnology Ltd.
First posted: 2025-01-27
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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:

  1. No CR was obtained after standard chemotherapy;
  2. CR was induced for the first time, but the duration of CR was less than 12 months;
  3. R/R B-ALL that does not work after the first or more remedial treatments;
  4. 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.

Primary outcomes:
measure: Dose-limiting toxicity (DLT)
timeFrame: Up to 28 days after Treatment
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Up to 2 years after Treatment
Secondary outcomes:
measure: Duration of remission ,DOR
timeFrame: Up to 1 years after CAR-T infusion
measure: Overall survival, OS
timeFrame: Up to 2 years after Treatment
measure: Event-free survival (EFS)
timeFrame: Up to 1 years after CAR-T infusion
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The first affiliated hospital of medical college of zhejiang university
state: Zhejiang
Study officials:
affiliation: Zhejiang University
name: He Huang, MD
role: PRINCIPAL_INVESTIGATOR
References: