B-cell Acute Lymphoblastic Leukemia
Conditions
Keywords
CD19 CAR-T
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.
Interventions
BIOLOGICALCD19 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
Sponsors
Yake Biotechnology Ltd.
Zhejiang University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-limiting toxicity (DLT) | Up to 28 days after Treatment | Adverse events assessed according to NCI-CTCAE v5.0 criteria |
| Incidence of treatment-emergent adverse events (TEAEs) | Up to 2 years after Treatment | Incidence of treatment-emergent adverse events \[Safety and Tolerability\] |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of remission ,DOR | Up to 1 years after CAR-T infusion | The time from CR/CRi and PR to disease relapsed or death due to disease progression after CAR-T infusion |
| Overall survival, OS | Up to 2 years after Treatment | After transplantation until death from any cause. |
| Event-free survival (EFS) | Up to 1 years after CAR-T infusion | defined as the time from the date of receiving the infusion to the date of treatment failure (failure to achieve CR/CRh/CRi/MLFS/PR after both efficacy assessments), or relapse (hematologic relapse or extramedullary relapse after CR/CRh/CRi), or death from any cause, whichever occurs first. When an EFS event was Ineffective Therapy, the primary analysis of EFS was performed on a 1-day basis (ie, time to treatment received as the event). For a more comprehensive assessment, sensitivity analyses could be performed using the actual date of treatment failure, end of treatment, or start of next-line anti-leukemia therapy as the end of EFS for treatment failure, respectively. |
Countries
China
Contacts
Primary ContactHe Huang, MD
Backup ContactYongxian Hu, MD
Outcome results
None listed