Clinical trial NCT03029338: CD19 CAR T Cells in Patients With Relapsed or Refractory CD19 Positive B-cell Lymphoma
Official title: CD19 CAR T Cells in Patients With Relapsed or Refractory CD19 Positive B-cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lymphomas Non-Hodgkin's B-Cell
Relapse
Keywords: lymphoma
non-hodgkin
B-cell
CD19 CAR T cells
refractory
relapse
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
Collaborators: name: Juventas Cell Therapy Ltd.
First posted: 2017-01-24
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of patients with adverse events
timeFrame: 2 years
Secondary outcomes:
measure: Severity of the adverse events
timeFrame: 2 years
measure: Response rate
timeFrame: 12 months
measure: Progression-free survival(PFS)
timeFrame: 2 years
measure: Persistence of CAR T cells in vivo
timeFrame: 2 years
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital
Study officials:
affiliation: Institute of Hematology & Blood Diseases Hospital, China
name: Dehui Zou, Dr.
role: PRINCIPAL_INVESTIGATOR
References: