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

Sponsor

Shanghai GeneChem Co., Ltd. (Industry)

Overall Status

Unknown status

CT.gov ID

NCT02672501

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia, B-Cell	Drug: anti-CD19-CAR-T cells	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Study Start Date :

Jan 1, 2016

Anticipated Primary Completion Date :

Jun 1, 2018

Anticipated Study Completion Date :

Dec 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	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 Other Names: 2nd CAR-T

Arm

Intervention/Treatment

Experimental: 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.

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

Other Names:

2nd CAR-T

Outcome Measures

Primary Outcome Measures

Number of patients with adverse event [6 weeks]
asverse event is evaluated with CTCAE, version 4.0

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)