Non-hodgkin Lymphoma,B Cell
Conditions
Keywords
CD19, CAR-T, TriCAR-T-CD19, non-Hodgkin lymphoma, NHL
Brief summary
This is a single arm, open-label, single-center, phase 1/2 study, to determine the safety and efficacy of TriCAR-T-CD19, an autologous tri-functional anti-CD19 chimeric antigen receptor (CAR)-positive T cell therapy, in refractory/Relapsed Non-Hodgkin Lymphoma (NHL).
Detailed description
The tri-functional anti-CD19 chimeric antigen receptor contains an anti-CD19 scFv, a PD-L1 blocker, and a cytokine complex, enabling the TriCAR-T-CD19 to simultaneously targeting the CD19 positive NHL，blocking the inhibitory PD-L1 signal and stimulating T/NK cell activation and expansion.
Interventions
BIOLOGICALTriCAR-T-CD19
A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by a single infusion of CAR transduced autologous T cells administered intravenously at a target dose of 0.5-1 x 10\^6 CAR+ T cells/kg
Sponsors
Hunan Provincial People's Hospital
Timmune Biotech Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 68 Years
Healthy volunteers
No
Inclusion criteria
1. All subjects must personally sign and date the consent form before initiating any study specific procedures or activities; 2. All subjects must be able to comply with all the scheduled procedures in the study; 3. Histologically or cytologically confirmed CD19 positive non-Hodgkin lymphoma; 4. Chemotherapy-refractory disease, defined as one or more of the following: Relapsed in 6 months after most recent therapy; Progressive disease in the standard R-CHOP or CHOP chemotherapy; Disease progression or relapsed in ≤12 months of ASCT (must have biopsy proven recurrence in relapsed subjects); If salvage therapy is given post-ASCT, the subject must have had no response to or relapsed after the last line of therapy. 5. No available standard therapy; 6. At least one measurable lesion per revised IWG Response Criteria; 7. Aged 18 to 68 years; 8. Expected survival ≥12 weeks; 9. Eastern cooperative oncology group (ECOG) performance status of ≤2; 10. Systematic usage of immunosuppressive drug or corticosteroid must have been stopped for more than 4 weeks; 11. All other treatment induced adverse events must have been resolved to ≤grade 1; 12. Laboratory tests must fulfill the following criteria: ANC ≥ 1000/uL, HGB \>70g/L, Platelet count ≥ 50,000/uL, Creatinine clearance ≤1.5 ULN, Serum ALT/AST ≤2.5 ULN, Total bilirubin ≤1.5 ULN (except in subjects with Gilbert's syndrome); 13. Female must be not pregnant during the study.
Exclusion criteria
1. History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) or follicular lymphoma unless disease free for at least 3 years; 2. History of allogeneic stem cell transplantation; 3. Prior other CAR therapy or other genetically modified T cell therapy; 4. Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management. Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active treatment; 5. Subjects with detectable cerebrospinal fluid malignant cells, or brain metastases, or with a history of CNS lymphoma, cerebrospinal fluid malignant cells or brain metastases; 6. Lactating women; 7. Active infection with hepatitis B (HBsAG positive) or hepatitis C virus (anti-HCV positive); 8. Subjects need systematic usage of corticosteroid; 9. History of any gene therapy; 10. Subjects need systematic usage of immunosuppressive drug; 11. Known history of infection with HIV; 12. Planed operation, history of other related disease, or any other related laboratory tests restrict patients for the study; 13. Other reasons the investigator think the patient may not be suitable for the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety (Incidence of treatment-related adverse events as assessed by CTCAE v4.0) | 30 Days | Incidence of treatment-related adverse events as assessed by CTCAE v4.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete response rate[CR] (Complete response rate per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma) | 12 months | Complete response rate per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma |
| Partial response rate [PR] (Partial response rate per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma) | 12 months | Partial response rate per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma |
| Duration of Response （The time from response to relapse or progression） | 12 months | The time from response to relapse or progression |
| Progression Free Survival（The time from the first day of treatment to the date on which disease progresses.） | 12 months | The time from the first day of treatment to the date on which disease progresses. |
| Overall Survival（The number of patient alive, with or without signs of cancer） | 24 months | The number of patient alive, with or without signs of cancer |
Countries
China
Contacts
Primary ContactMing Zhou
Backup ContactBin Gao
Outcome results
None listed