A Clinical Research of CAR T Cells Targeting CD19 Positive Malignant B-cell Derived Leukemia and Lymphoma

Phase 1

• Conditions: Leukemia; Lymphoma
• Interventions: Biological: Chimeric Antigen Receptor Modified T cells Targeting CD19

• Registration Number: NCT02349698
• Lead Sponsor: Southwest Hospital, China

Brief Summary

The main purpose of this research is to verify the safety of CD19 targeted chimeric antigen receptor T cells and to determine the proper dosage of CAR T cells infused.

Detailed Description

Nowadays refractory or relapsed leukemia/lymphoma lacks effective treatment. Innovative therapy is urgently required. Chimeric antigen receptor (CAR)-modified T cells have demonstrated great successes in treating even late stage cluster of differentiation antigen 19 (CD19) positive B cell malignancies. To design better CAR T cells, we have developed new CD19 CARs. Preclinical studies have demonstrated effective killing of CD19 target cells. In this study, the CD19 CARs, will be evaluated in CD19 positive leukemia/lymphoma patients. The primary goal is to confirm its adverse effects including cytokine storm response and any other adverse effects. In addition, tumor targeting and disease status after treatment will also be evaluated.

Study Timeline

• Study Start: 2014-12
• Study First Submitted: 2015-01-25
• Study First Submitted QC: 2015-01-28
• Study First Posted: 2015-01-29
• Status Verified: 2019-06
• Last Update Submitted: 2019-06-23
• Last Update Posted: 2019-06-25
• Primary Completion: 2022-12
• Study Completion: 2023-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

1. Relapsed or refractory B cell derived acute lymphoblastic leukemia(ALL), chronic lymphocytic leukemia(CLL) and non-hodgkin lymphoma.
2. KPS>60.
3. Life expectancy>3 months.
4. Gender unlimited, age from 4 years to 75 years.
5. Disease progresses but reserves reaction to recent treatments.
6. Patients who have failed at least one line of a standard treatment.
7. No serious mental disorder.
8. Patients must have adequate cardiac function(no cardiac disease, LVEF≥40% ), adequate pulmonary function as indicated by room air oxygen saturation of >94%, and adequate renal function(Cr≤133umol/L).
9. No other serious diseases(autoimmune disease, immunodeficiency etc.).
10. No other tumors.
11. Patients volunteer to participate in the research.

Exclusion Criteria

1. HIV affected.
2. Patients are allergic to cytokines.
3. Central nervous system leukemia within 28 days.
4. Uncontrolled active infection.
5. Acute or chronic GVHD.
6. Treated with T cell inhibitor.
7. Pregnancy and nursing females.
8. Other situations we think improper for the research.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Chronic Lymphcytic Leukemia	Chimeric Antigen Receptor Modified T cells Targeting CD19	Chronic lymphocytic leukemia with chimeric antigen receptor modified T cells targeting CD19.
Non-Hodgkin Lymphoma	Chimeric Antigen Receptor Modified T cells Targeting CD19	Non-hodgkin lymphoma treated with chimeric antigen receptor modified T cells targeting CD19.
Acute Lymphoblastic Leukemia	Chimeric Antigen Receptor Modified T cells Targeting CD19	Acute lymphoblastic leukemia treated with chimeric antigen receptor modified T cells targeting CD19.

Primary Outcome Measures

Name	Time	Method
Adverse events of each patient.	3 years	Determine the toxicity profile of the CD19 targeted CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.

Secondary Outcome Measures

Name	Time	Method
Maximum tolerated dose (MTD) of CD19 targeted CAR T cells.	4 weeks	To confirm the maximum tolerated dose of CD19 targeted CAR T cells.
Efficacy of anti-CD19 CAR T cells assessed by the ability of CAR T cells to kill leukemia/lymphoma cells	12 weeks
Survival time of Anti-CD19 CAR T cells in vivo.	3 years	To evaluate the presence of circulating CAR T cells with flow cytometry and real time PCR in patient blood.

Trial Locations

Locations (1)

Southwest Hospital of Third Millitary Medical University; 🇨🇳 Chongqing, Chongqing, China