A Study to Assess CD19-targeted Immunotherapy T Cells in Patients With Relapsed or Refractory CD19+ B Cell Leukemia

Leukemia, B-Cell Clinical Trial

Official title:

Open-labeled, Uncontrolled, Single-arm Pilot Study to Evaluate Cellular Immunotherapy Using CD19-targeted Chimeric Antigen Receptor Engineered T Cells in Patients With Relapsed or Refractory CD19+ B Cell Leukemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02672501
• Other study ID #: Genechem
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: January 25, 2016
• Last updated: February 1, 2016
• Start date: January 2016
• Est. completion date: December 2019

Study information

• Verified date: February 2016
• Source: Shanghai GeneChem Co., Ltd.
• Contact: Jianmin Yang, Doctor
• Phone: 86-18317172636
• Email: yangjianmin[@]csco.org.cn
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

In the conventional treatment options, B cell leukemia could be treated with chemotherapy drugs or HSCT. But chemotherapy could barely cured leukemia. And HSCT is often limited by lacking of HLA-matched donors, even if those patients who received HSCT still could be relapsed. And now, chimeric antigen receptor modified T cell infusion maybe an effective treatment to solve these problems. The investigators use a 2nd CAR- T with the optimized hinge and transmembrane domain to treat patients with relapsed or refractory B cell leukemia, including relapsed cases after HSCT. The purpose of this study is to assess the safety and efficacy of this 2nd CAR-T cells. At the same time, evaluating the possible and clinical responses of using donor-derived T cells engineered CAR-T cells.

Detailed Description: This study is being conducted to assess anti-CD19-CAR-T cells safety and efficacy in treating patients with B cell leukemia. The investigators constructed a 2nd CAR, CD19 as target protein, 4-1BB as co-stimulator. And optimized the spatial conformation by a suitable hinge & transmembrane domain sequences. The source of T cells for CAR-T is from two aspects, one is autologous, the other is donor-derived (only suitable for patients received HSCT before and relapsed). The infusion dose is (1-5)×106 CAR positive T cells/kg, and the specific cells numbers depend on the situation of individual CAR-T cells preparation.

Description:

This study is being conducted to assess anti-CD19-CAR-T cells safety and efficacy in treating patients with B cell leukemia. The investigators constructed a 2nd CAR, using CD19 as target, using 4-1BB as co-stimulator, and optimized the spatial conformation by a suitable hinge and transmembrane domain sequences. The source of T cells used to prepare CAR-T could be either autologous, or donor-derived (only suitable for patients received HSCT before and relapsed). The infusion dose is (1-5)×106 CAR positive T cells/kg, and the specific cells numbers depends on the situation of individual CAR-T cells preparation.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 2019
• Est. primary completion date: June 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 70 Years

Eligibility

Inclusion Criteria:

• Patients with CD19+ B-cell leukemia as comfirmed by Flow Cytometry

• Age: 1-70 years old

• Expected survival > 12 weeks

• Creatinine < 2.5 mg/dl

• ALT/AST < 3x normal

• Bilirubin <2.0 mg/dl

• Sucessful test expansion of T-cells

• Adequate venous access for apheresis, and no other contraindications for leukapheresis

• Voluntary informed consent is given

Exclusion Criteria:

• Pregnant or lactating women

• Uncontrolled active infection

• Active hepatitis B or hepatitis C infection

• Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary

• Previously treatment with any gene therapy products

• Feasibility assessment during screening demonstrates<30% transduction of target lymphocytes, or insufficient expansion (<5-fold) in response to CD3/CD28 costimulation

• Active central nervous system leukemia

• Any serious, uncontrolled diseases (including, but not limit to, unstable angina pectoris, congestive heart failure, grade ? or ? cardiac disease, serious arrhythmia, liver and kidney disorders or metabolic diseases)

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, B-Cell
• Leukemia, Lymphocytic, Chronic, B-Cell

Intervention

Drug:
• anti-CD19-CAR-T cells
a 2nd CAR, CD19 as target protein, 4-1BB as co- stimulator, and optimized the spatial conformation by a suitable hinge & transmembrane domain sequences

Locations

Country	Name	City	State
China	Shanghai Changhai Hospital,The Second Military Medical University	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai GeneChem Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients with adverse event	asverse event is evaluated with CTCAE, version 4.0	6 weeks	Yes
Secondary	Number of patients with tumor response	summarize tumor response by overal response rates	8 weeks	No
Secondary	Detection of transferred T cells in the circulation using quantitative -PCR		6 weeks	No