CD19 CAR T Cells in Patients With Relapsed or Refractory CD19 Positive B-cell Lymphoma

Phase 1

Completed

• Conditions: Relapse; Lymphomas Non-Hodgkin's B-Cell
• Interventions: Biological: CD19 CAR T cells

• Registration Number: NCT03029338
• Lead Sponsor: Institute of Hematology & Blood Diseases Hospital, China

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.

Study Timeline

• Study First Submitted: 2017-01-20
• Study First Submitted QC: 2017-01-20
• Study First Posted: 2017-01-24
• Study Start: 2017-06-08
• Primary Completion: 2019-05-22
• Study Completion: 2021-06-22
• Status Verified: 2022-01
• Last Update Submitted: 2022-01-24
• Last Update Posted: 2022-01-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CD19 CAR T cells	CD19 CAR T cells	CD19 CAR T cells 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.

Primary Outcome Measures

Name	Time	Method
Number of patients with adverse events	2 years

Secondary Outcome Measures

Name	Time	Method
Response rate	12 months
Progression-free survival(PFS)	2 years
Severity of the adverse events	2 years
Persistence of CAR T cells in vivo	2 years

Trial Locations

Locations (1)

Institute of Hematology & Blood Diseases Hospital; 🇨🇳 Tianjin, China