Safety and Efficacy Evaluation of IM19 CAR-T Cells

Study Overview
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Brief Summary
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Assessment of the Safety and Feasibility of Administering T Cells Expressing an Anti-CD19 Chimeric Antigen Receptor to Patients With CD19+ B-cell leukemia or CD19+ B-all.

Detailed Description
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Assessment of the Safety and Feasibility of Administering T Cells Expressing an Anti-CD19 Chimeric Antigen Receptor to Patients With CD19+ B-cell leukemia or CD19+ B-ALL patients and determine the MTD,LTD and the best dosage.

Official Title
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Safety and Efficacy Evaluation of IM19 CAR-T Cells on Refractory or Relapsed B-ALL Patients

Conditions
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Leukemia

Intervention / Treatment
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* Biological: IM19 CAR-T


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with CD19+ leukemia, meeting the following criteria At least 2 prior combination chemotherapy regimens (not including single agent monoclonal antibody (Rituximab) therapy) Less than 1 year between last chemotherapy and progression Not eligible or appropriate for allo-HSCT To be aged 4 to 65 years Estimated survival of ≥ 6 months, but ≤ 2 years ECOG score ≤2 Relapse after auto-HSCT Women of childbearing potential must have a urine pregnancy test taken and proven negative prior to the treatment. All patients agree to use reliable methods of contraception during the trial period and until follow-up for the last time. Voluntary participation in the clinical trials and sign the informed consent. Exclusion Criteria: History of epilepsy or other CNS disease Patients have GVHD, which needs treatment with immunosuppressive agents Patients with prolonged QT interval or severe heart disease Patients in pregnancy or breast-feeding period 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 ALT /AST>3 x normal value; Creatinine> 2.5 mg/dl; Bilirubin >2.0 mg/dl Any uncontrolled medical disorders that the researchers consider are not eligible to participate the clinical trial HIV infection Any situation that would increase dangerousness of subjects or disturb the outcome of the clinical study according to the researcher's evaluation.

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IM19 CART<br>A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by a single infusion of IM19CART cells administered intravenously. | Biological: IM19 CAR-T<br>* All patients will be treated with fludarabine and cyclophosphamide for 3 days,then,CAR-T cells expressing CD19 CAR will be infused 24-96 hours later.<br>* Other names: fludarabine，cyclophosphamide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of study related adverse events | defined as >= Grade 3 signs/symptoms, laboratory toxicities, and clinical events) that are possibly, likely, or definitely related to study treatment Adverse events assessed according to NCI-CTCAE v4.0 criteria 2. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate | An objective response is defined as: (1) a morphologic complete response (CR) or (2) a complete response with incomplete recovery of counts (CRi) (based on NCCN guidelines (National Comprehensive Cancer Network (NCCN), 2014) or (3) a negative minimal residual disease assessed by flow cytometry | 2 years |