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

Phase 1

• Conditions: Leukemia, B-Cell
• Interventions: Drug: anti-CD19-CAR-T cells

• Registration Number: NCT02672501
• Lead Sponsor: Shanghai GeneChem Co., Ltd.

Brief 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.

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, 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.

Study Timeline

• Study Start: 2016-01
• Study First Submitted: 2016-01-25
• Status Verified: 2016-02
• Study First Submitted QC: 2016-02-01
• Last Update Submitted: 2016-02-01
• Study First Posted: 2016-02-03
• Last Update Posted: 2016-02-03
• Primary Completion: 2018-06
• Study Completion: 2019-12

Recruitment & Eligibility

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

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 Ш or Ⅳ cardiac disease, serious arrhythmia, liver and kidney disorders or metabolic diseases)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
anti-CD19-CAR-T cells	anti-CD19-CAR-T cells	patients receive chemotherapy(CF, cyclophosphamide and Fludarabine) on day -6 to day -1, then infusied with anti-CD19-CAR-T cells transduced with lentivirus on day 0 in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Number of patients with adverse event	6 weeks	asverse event is evaluated with CTCAE, version 4.0

Secondary Outcome Measures

Name	Time	Method
Number of patients with tumor response	8 weeks	summarize tumor response by overal response rates
Detection of transferred T cells in the circulation using quantitative -PCR	6 weeks

Trial Locations

Locations (1)

Shanghai Changhai Hospital，The Second Military Medical University; 🇨🇳 Shanghai, Shanghai, China