Lymphomas Non-Hodgkin's B-Cell, Relapse
Conditions
Keywords
lymphoma, non-hodgkin, B-cell, CD19 CAR T cells, refractory, relapse
Brief summary
In this single-center, open-label, no control, prospective clinical trial, a total of 10 relapsed or refractory CD19 positive B-cell Non-Hodgkin Lymphoma (NHL) patients will be enrolled.CD19 CAR T cells(total dose of 2×10\^6/kg-1×10\^7/kg) will be intravenously infused to patient in a three-day split-dose regimen: 10% on day 0, 30% on day 1 and 60% on day 2. The purpose of current study is to determine the clinical efficacy and safety of CD19 CAR T cells in patients with relapsed or refractory CD19 positive B-cell lymphoma.
Detailed description
In this single-center, open-label, nonrandomized, no control, prospective clinical trial, a total of 10 relapsed or refractory CD19+ B-cell Non-Hodgkin Lymphoma (NHL) patients will be enrolled. CD19 CAR T cells transduced with a lentiviral vector to express anti-CD19 scFv TCRζ:4-1BB, will be administered by i.v. injection in a three-day split-dose regimen: 10% on day 0, 30% on day 1 and 60% on day 2. Side effects of CD19 CAR T cells therapy will be monitored. The purpose of current study is to determine the clinical efficacy and safety of CD19 CAR T cells therapy in patients with relapsed or refractory CD19 positive B-cell lymphoma.
Interventions
BIOLOGICALCD19 CAR T cells
CD19 CAR T cells was transduced with a lentiviral vector to express anti-CD19 scFv TCRζ:4-1BB.
Sponsors
Institute of Hematology & Blood Diseases Hospital, China
Juventas Cell Therapy Ltd.
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
* Patients aged 18 to 70 years with relapsed or refractory CD19 positive B-cell lymphoma. * Eastern Cooperative Oncology Group (ECOG) Performance status 0-2. * Adequate end organ function as defined by: Total bilirubin ≤ 1.5 x upper limit of normal（ULN）; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN; Creatinine ≤ 1.5 x ULN or any serum creatinine level associated with a measured or calculated creatinine clearance of ≥ 40ml/min. * Male and female of reproductive potential must agree to use birth control during the study and for at least 6 weeks post study. * Patients should sign informed consent form.
Exclusion criteria
* Patients with central nervous system involvement by lymphoma. * Prior chemotherapy within 2 weeks before enrollment with the following exceptions: steroids, hydroxyurea, oral mercaptopurine, methotrexate, vincristine and thioguanine are permitted within 2 weeks of enrollment as maintenance or to reduce tumor load. * Prior allogeneic hematopoietic stem cell transplant (HSCT) ≤ 4 months before enrollment. Patients must have completed immunosuppression therapy prior to enrollment. At enrollment, patients must not have≥ grade 2 acute GVHD, or either moderate or severe limited chronic GVHD, or extensive GVHD of any severity. * Known systemic vasculitides, primary or secondary immunodeficiency(such as HIV infection or severe inflammatory disease). * Major surgery within 4 weeks before enrollment. * Impaired cardiac function:Ejection fraction ≤45 % on MUGA scan. QTc interval \> 450msecs on baseline ECG. Myocardial infarction within 6 months prior to starting study; other clinically significant heart disease (e.g. unstable angina, congestive heart failure or uncontrolled hypertension, uncontrolled arrhythmias). * Administration of live vaccine ≤ 4 weeks before enrollment. * Other concurrent severe and/or uncontrolled medical conditions: Patients with another primary malignant disease, except those that do not currently require treatment; acute or chronic liver, pancreatic or severe renal disease; another severe and/or life-threatening medical disease.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of patients with adverse events | 2 years |
Secondary
| Measure | Time frame |
|---|---|
| Severity of the adverse events | 2 years |
| Response rate | 12 months |
| Progression-free survival(PFS) | 2 years |
| Persistence of CAR T cells in vivo | 2 years |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORDehui Zou, Dr.
Institute of Hematology & Blood Diseases Hospital, China
Outcome results
None listed