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

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.

Study Overview

• Status: Unknown
• Conditions: B Cell Lymphoma
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: Fludarabine; Biological: CART-19

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 Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China
      • Recruiting
      • Henan Cancer Hospital
      • Contact: Yongping Song; Phone Number: -86-13521186987; Email: ph200811@163.com
      • Contact: Yongping Song
      • Principal Investigator: Yongping Song, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Cyclophosphamide; patients will receive a standard pre-conditioning regime with cyclophosphamide 0.8-1.0g/m2/day IV for 2 days(Day-5 to day-4).; Drug: Fludarabine; Fludarabine 25 mg/m2/day IV for 3 days (Day-5 to day-3).; Biological: CART-19; CART-19 cells will be administered using a split dose on day0(10%), 1(30%), and 2(60%) after completion of the chemotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
safety as assessed by the occurence of study related adverse events	monitor the occurence of study related adverse events	6 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Henan Cancer Hospital
• Collaborators: The Beijing Pregene Science and Technology Company, Ltd.
• Investigators: Study Director: Yongping Song, Henan Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2016
• Primary Completion (Anticipated): July 1, 2018
• Study Completion (Anticipated): July 1, 2019

Study Registration Dates

• First Submitted: March 30, 2017
• First Submitted That Met QC Criteria: April 4, 2017
• First Posted (Actual): April 5, 2017

Study Record Updates

• Last Update Posted (Actual): April 5, 2017
• Last Update Submitted That Met QC Criteria: April 4, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine
• Other Study ID Numbers: HenanCH109

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No