Clinical trial NCT02672501: A Study to Assess CD19-targeted Immunotherapy T Cells in Patients With Relapsed or Refractory CD19+ B Cell Leukemia
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Leukemia, B-Cell
Keywords: immunotherapy
CAR-T
leukemia
Lead sponsor: Shanghai GeneChem Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2016-02-03
Enrollment: 30
Sex: ALL
Minimum age (years): 1
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Number of patients with adverse event
timeFrame: 6 weeks
Secondary outcomes:
measure: Number of patients with tumor response
timeFrame: 8 weeks
measure: Detection of transferred T cells in the circulation using quantitative -PCR
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Changhai Hospital，The Second Military Medical University
state: Shanghai
Study officials:
affiliation: Shanghai Changhai Hospital，The Second Military Medical University
name: Jianmin Yang, Doctor
role: PRINCIPAL_INVESTIGATOR
References: