The Safety and Efficacy of CART-19 Cells in Relapse and Refractory Patients With CD19+ B-cell Lymphoma

Phase 1

• Conditions: B Cell Lymphoma
• Interventions: Drug: Cyclophosphamide; Drug: Fludarabine; Biological: CART-19

• Registration Number: NCT03101709
• Lead Sponsor: Henan Cancer Hospital

Brief Summary

This is a clinical study to observe the safety and feasibility of chimeric antigen receptor 19 (CART-19) cells in relapsed and refractory patients with CD19+ B cell lymphoma.

Detailed Description

This is a study for the patients with B cell lymphoma. Subjects will be staged and the suitability of their T cells for CART-19 manufacturing will be determined at entry phase. Subjects will be collected their T cells and modify them, the modification is a genetic change, that CD19:4-1BB: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 to assess ssess the safety and feasibility of CART-19 cells in the patients with relapsed and refractory CD19+ B cell lymphoma.

Study Timeline

• Study Start: 2016-08
• Status Verified: 2017-03
• Study First Submitted: 2017-03-30
• Study First Submitted QC: 2017-04-04
• Last Update Submitted: 2017-04-04
• Study First Posted: 2017-04-05
• Last Update Posted: 2017-04-05
• Primary Completion: 2018-07
• Study Completion: 2019-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

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;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CART-19	CART-19	patients will receive a pre-conditioning with cyclophosphamide and fludarabine before infusion of CART-19 cells. The CART-19 cells are to be administered on day0,day1,day2.
CART-19	Cyclophosphamide	patients will receive a pre-conditioning with cyclophosphamide and fludarabine before infusion of CART-19 cells. The CART-19 cells are to be administered on day0,day1,day2.
CART-19	Fludarabine	patients will receive a pre-conditioning with cyclophosphamide and fludarabine before infusion of CART-19 cells. The CART-19 cells are to be administered on day0,day1,day2.

Primary Outcome Measures

Name	Time	Method
safety as assessed by the occurence of study related adverse events	6 months	monitor the occurence of study related adverse events

Secondary Outcome Measures

Name	Time	Method
duration of CART-19	2 years	Determine duration of in vivo survival of CART-19 cells
efficacy assessed by anti-tumor activity of CART-19 cells	2 years	anti-tumor activity of CART-19 cells will be determined in a follow-on study

Trial Locations

Locations (1)

Henan Cancer Hospital; 🇨🇳 Zhengzhou, Henan, China