B Cell Lymphoma
Conditions
Brief summary
This is a clinical study to observe the maximum tolerated dose (MTD) and the safety and feasibility of chimeric antigen receptor 19 (CD19 CART) cells in relapsed and refractory patients with CD19+ B cell lymphoma.
Detailed description
This is a study for the patients with B cell lymphoma. Maximum tolerated dose climbing test is expected into the group of 9 cases of patients. And Phase II expected into the group of 11 subjects, selected the above safe dose, carrying out a research into the clinical effectiveness. Subjects will be collected their T cells and modify them, the modification is a genetic change, that CD19:4-1BB:CD28:CD3 modified T cells, in order to tells the T cells to recognize their target tumor cells and potentially kill them, but not other normal cells in the subject's body. The CART cells will then be expanded in vitro and then administered to subjects. The purpose of this study is observe the MTD and to assess the safety and feasibility of CART cells in the patients with relapsed and refractory CD19+ B cell lymphoma.
Interventions
DRUGFludarabine
Fludarabine 30 mg/m2/day IV for 3 days.
DRUGCyclophosphamide
patients will receive a standard pre-conditioning regime with cyclophosphamide 0.8g/m2/day IV for 2 days.
BIOLOGICALCD19 CART
CD19 CART cells will be administered using a split dose on day0(10%), 1(30%), and 2(60%) after completion of the chemotherapy.
Sponsors
The Beijing Pregene Science and Technology Company, Ltd.
Shenzhen Second People's Hospital
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\. 18 years to 70 years, expected survival \> 3 months; * 2\. CD19 positive B-cell lymphoma; * 3\. KPS \>80; * 4\. Having at least one measurable lesions; * 5\. Cardiac function: 1-2 levels; Liver: TBIL≤3ULN，AST ≤2.5ULN，ALT ≤2.5ULN; kidney: Cr≤1.25ULN; bone marrow: WBC ≥ 3.0×109/L, Hb ≥90 g/L, PLT ≥ 80×109/L）; * 6\. No serious allergic constitution; * 7\. No other serous diseases that conflicts with the clinical program; * 8\. No other cancer history; * 9\. No serious mental disorder; * 10\. Informed consent is signed by a subject or his lineal relation.
Exclusion criteria
* 1\. Pregnant or lactating women; (female participants of reproductive potential must have a negative serum or urine pregnancy test); * 2\. Uncontrolled active infection, HIV infection, syphilis serology reaction positive; * 3\. Active hepatitis B or hepatitis C infection; * 4\. Recent or current use of glucocorticoid or other immunosuppressor; * 5\. With severe cardiac, liver, renal insufficiency, diabetes and other diseases; * 6\. Transaminase \>2.5ULN, Bilirubin \>3ULN，Creatinine\>1.25ULN * 7\. Participate in other clinical research in the past three months; previously treatment with any gene therapy products; * 8\. Researchers think of that does not fit to participate in the study, or other cases that affect the clinical trial results;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival | 2 years | — |
| objective response rate | 2 years | CR+PR |
| disease control rate | 2 years | CR+PR+SD |
| overall survival | 2 years | OS |
| safety as assessed by the occurence of study related adverse events | 6 months | monitor the occurence of study related adverse events |
| observe the maximum tolerated dose (MTD) | 2 months | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peripheral blood cytokines | 2 months | IL-6、IL-10、IFN-γ、TNF-α |
| subgroup of T cell | 2 years | CD3、CD4、CD8 |
| Determine duration of in vivo survival of CD19 CART cells | 2 years | CD19 CART vector sequences will be performed by Q-PCR |
Countries
China
Contacts
Primary Contactgeng tian
Outcome results
None listed