Non-hodgkin Lymphoma,B Cell
Conditions
Keywords
CAR-T, TriCAR-T, CD19-TriCAR-T, Non-hodgkin Lymphoma, NHL, CD19-CAR-T
Brief summary
This is a single arm, open-label, phase Ⅰ study, to determine the safety and efficacy of CD19-TriCAR-T, an autologous tri-functional anti- CD19 chimeric antigen receptor (CAR)-positive T cell therapy, in Refractory/ Relapsed CD19 Positive 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 CD19-TriCAR-T to simultaneously targeting the CD19 positive NHL cells，blocking the inhibitory PD-L1 signal and stimulating T/NK cell activation and expansion.
Interventions
BIOLOGICALCD19-TriCAR-T
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 0.1-1 x 10\^6 CAR+ T cells/kg body weight.
Sponsors
Timmune Biotech Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 69 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. At least one measurable lesion per revised IWG Response Criteria; 5. Aged 18 to 69 years; 6. Expected survival ≥12 weeks; 7. Eastern cooperative oncology group (ECOG) performance status of ≤2; 8. Systematic usage of immunosuppressive drug or corticosteroid must have been stopped for more than 4 weeks; 9. All other treatment induced adverse events must have been resolved to ≤grade 1; 10. 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);
Exclusion criteria
1. 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; 2. Patients with symptomatic central nervous system metastasis, intracranial metastasis, and cancer cells found in cerebrospinal fluid are not recommended to participate in this study. Symptom free or post-treatment stable disease or disappearance of lesions should not be excluded. The specific selection is ultimately determined by the investigator; 3. Lactating women; 4. Active infection with hepatitis B (HBsAG positive) or hepatitis C virus (anti-HCV positive); 5. Known history of infection with HIV; 6. Subjects need systematic usage of corticosteroid; 7. Subjects need systematic usage of immunosuppressive drug; 8. Planed operation, history of other related disease, or any other related laboratory tests restrict patients for the study; 9. 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 v4.03） | 24 months | Incidence of treatment-related adverse events as assessed by CTCAE v4.03 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Progression Free Survival （The time from the first day of treatment to the date on which disease progresses） | 24 months | The time from the first day of treatment to the date on which disease progresses |
| Complete response rate[CR] (Complete response rate per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma) | 24 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） | 24 months | Partial response rate per the revised International Working Group (IWG) Response Criteria |
| Duration of Response （The time from response to relapse or progression） | 24 months | The time from response to relapse or progression |
Countries
China
Contacts
Primary ContactHaifeng Lin
Backup ContactBin Gao, Dr.
Outcome results
None listed