Refractory B-Cell Non-Hodgkin Lymphoma, Refractory Leukemia
Conditions
Keywords
Modified CD19 CAR-T
Brief summary
This study aims to evaluate the safety and tolerance of modified CD19 CAR T cells in treating refractory/relapsed B-cell malignancies. CAR-T cells will be investigated as a single agent both in relapsed/refractory B-cell acute lymphoblastic leukaemia (B-ALL) and up to 60% of patients with B-cell non-Hodgkin's lymphoma (NHL).
Interventions
BIOLOGICALModified anti-CD19 CAR T cells
intravenous infusion
Sponsors
Liqun Zou
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female aged 18-70 years; 2. Estimated survival time ≥ 12 weeks; 3. Histologically confirmed diagnosis of CD19+ B-ALL or CD19+ B-NHL(meeting one of the following conditions): 1. Ineffectively or relapses after 2 or more remedial treatments 2. Relapse after auto-HSCT or unsuitable for auto-HSCT; 4. At least one assessable tumor lesion; 5. ECOG performance status 0 to 2; 6. Creatinine clearance rate≥ 60 ml/min, ALT and AST ≤ 2.5 times of upper limit of normal, total bilirubin ≤ 1.5 times of upper limit of normal; 7. Male and female of reproductive potential must agree to use birth control during the study and for at least 30 days post study; 8. Patients or their legal guardians volunteer to participate in the study and sign the informed consent.
Exclusion criteria
1. Patients with other uncontrolled malignancies; 2. Previously treated with any CAR-T cell product or other genetically-modified T cell therapy; 3. Patients with HIV infection, hepatitis B (HBsAg positive) or hepatitis C（anti-HCV positive); 4. Patients with central nervous system involvement by lymphoma ,malignant cells in cerebrospinal fluid or history of brain metastasis; 5. Patients with atrial or ventricular involvement by B-cell malignancies; 6. Patients with tumor mass require urgent treatment, such as ileus or vascular compression; 7. Patients with severe disease or other uncontrolled diseases that were not suitable for this trial, such as coronary heart disease, angina pectoris, myocardial infarction, arrhythmia, cerebral thrombosis, cerebral hemorrhage, grade 2-3 hypertension; 8. Unstable pulmonary embolism, deep venous embolism, or other major arterial/venous thromboembolism events occurred within 30 days prior to randomization. If patients receive anticoagulant therapy, the treatment dose must be stable prior to randomization; 9. Any situations that the investigators believes were not suitable for this trial; 10. Long-term use of immunosuppressive agents after organ transplantation, except for the patients recently or currently receiving inhaled steroids; 11. Pregnant(or lactation) women; 12. Patients with severe active infections(excluding simple urinary tract infection and bacterial pharyngitis)within 30 days prior to randomization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment-emergent adverse events [Safety and Tolerability] | Up to 5 years after modified CD19 CAR-T cells infusion | Adverse events assessed according to NCI-CTCAE v5.0 criteria |
| Dose-limiting toxicity (DLT) | Baseline up to 28 days after modified CD19 CAR-T cells infusion | Adverse events assessed according to NCI-CTCAE v5.0 criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| B-cell malignancies, Overall response rate(ORR) | 3 months, 6 months | Assessment of ORR(ORR=CR+PR) |
| B-cell malignancies, Overall survival | Up to 2 years after modified CD19 CAR-T cells infusion | From the first infusion of modified CD19 CAR-T cells to death or the last visit |
| B-cell malignancies, progression-free survival（PFS） | Up to 2 years after modified CD19 CAR-T cells infusion | From the first infusion of modified CD19 CAR-T cells to the occurrence of any event, including death, relapse, disease progression, and the last visit |
| B-cell malignancies, disease control rate (DCR) | Month 6,12,18 and 24 | Assessment of DCR(DCR=CR+PR+SD) |
Countries
China
Contacts
Primary Contactpei shu, MD
Backup Contactfuchun guo, MD
Outcome results
None listed