Acute Lymphoblastic Leukemia,B-Cell, Non-hodgkin Lymphoma,B Cell
Conditions
Keywords
CD19-BAFF CAR-T
Brief summary
Clinical Trial for the safety and efficacy of CD19-BAFF CAR-T cells therapy for refractory/relapsed B-cell acute lymphoblastic leukemia and B-cell non-Hodgkin lymphoma.
Detailed description
In this study, 20 patients with relapsed refractory B-cell ALL and B-cell NHL were proposed to undergo CD19-BAFF CAR-T cell therapy. Under the premise that its safety has been clarified in previous studies, further observation and evaluation of the effectiveness of CD19-BAFF CAR-T cell therapy for relapsed refractory B-cell ALL and B-cell NHL; At the same time, on the basis of expanding the sample size, more safety data on CD19-BAFF CAR-T cell treatment for relapsed refractory B-cell ALL and B-cell NHL were accumulated, including rare and delayed complications.
Interventions
BIOLOGICALCD19-BAFF Targeted CAR T-cells
Each subject receive CD19-BAFF 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\. Gender unlimited，18\< Age; * 2\. Patients diagnosed with B-cell acute lymphoblastic leukemia through histological or immunophenotyping tests; The clear diagnosis of B-cell non Hodgkin's lymphoma by cellular or histopathological examination mainly includes diffuse large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma * 3\. Relapsed or refractory CD19+ B-ALL (meeting one of the following conditions): 1. CR not achieved after standardized chemotherapy; 2. CR achieved following the first induction, but CR duration is less than 12 months; 3. Ineffectively after first or multiple remedial treatments; 4. 2 or more relapses; * 4\. The number of primordial cells (lymphoblast and prolymphocyte) in bone marrow is \>5% (by morphology), and/or \>1% (by flow cytometry); * 5\. Philadelphia-chromosome-negative (Ph-) patients; or Philadelphia-chromosome-positive (Ph+) patients who cannot tolerate TKI treatments or do not respond to 2 TKI treatments; * 6\. Relapsed or refractory B-NHL (meeting one of the following conditions): 1. No response or relapse after second-line or above chemotherapy regimens; 2. Primary drug resistance; 3. Relapse after auto-HSCT; * 7\. At least one assessable tumor lesion per Lugano 2014 criteria; * 8\. Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit of normal, creatinine ≤ 176.8 umol/L; * 9\. Echocardiogram shows left ventricular ejection fraction (LVEF) ≥ 50%; * 10\. No active infection in the lungs, blood oxygen saturation in indoor air is ≥ 92%; * 11\. Estimated survival time ≥ 3 months; * 12\. ECOG performance status 0 to 2; * 13\. Patients or their legal guardians volunteer to participate in the study and sign the informed consent.
Exclusion criteria
* 1\. History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular hemorrhagic diseases; * 2\. Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past; * 3\. Pregnant/lactating women, or male or female patients with fertility who are unwilling to take effective contraceptive measures during the study period or at least 6 months after the last cell infusion * 4\. Patients with HIV infection; * 5\. Active infection of hepatitis B virus or hepatitis C virus; * 6\. The proiferation rate is less than 5 times response to CD3/CD28 co-stimulation signal; * 7\. Other uncontrolled diseases that were not suitable for this trial; * 8\. Individuals who have received CAR-T therapy, CAR-NK therapy, or any other gene modified cell therapy product within 6 months; * 9\. Any situations that the investigator believes may increase the risk of patients or interfere with the results of study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-limiting toxicity (DLT) | Up to 28 years 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 |
|---|---|---|
| Overall response rate ,ORR | Up to 12 weeks after CAR-T infusion | The proportion of patients with CR (complete response) /CRi (complete response with incomplete blood cell recovery) and PR (partial response). |
| 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 |
| Event-free survival, EFS | Up to 1 years after CAR-T infusion | The time from first achieving CR/CRi to relapse or death |
| Overall survival, OS | Up to 1 years after CAR-T infusion | The time from CAR-T infusion to death due to any cause |
Countries
China
Contacts
Primary ContactHe Huang, MD
Backup ContactYongxian Hu, MD
Outcome results
None listed