Phase I Study of CD19-CAR-T2 Cells for Patients With Chemotherapy Resistant or Refractory CD19+ Acute Leukemia

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of chimeric antigen receptor 19 (CD19-CAR-T2 Cells) infusions in patients with chemotherapy resistant or refractory CD19+ acute Leukemia.

Official Title
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CD19-CAR-T2 Cells for Relapse/Refractory CD19 Positive Acute Leukemia-a Phase I Trial

Conditions
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Acute Leukemia

Intervention / Treatment
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* Biological: CD19-CAR-T2 Cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with relapsed and/or refractory CD19 positive B-cell acute leukemia Eastern Cooperative Oncology Group (ECOG) performance status 《 3 ALT/ AST 《 3x normal Bilirubin < 2.0 mg/dl Creatinine < 2.5 mg/dl and less than 2.5x normal for age LVEF》 45% Accept white blood cell collection Provide informed consent Exclusion Criteria: Previous treatment with investigational gene or cell therapy medicine products Solitary extramedullary relapse Active hepatitis B , hepatitis C or HIV infection Uncontrolled active infection Presence of grade 2-4 acute or extensive chronic GVHD Active CNS involvement: epilepsy, paresis, aphasia, stroke, severe head trauma, Dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, uncontrolled mental illness, etc. Any uncontrolled active medical disorder that would preclude participation as outlined. Received non-diagnostic purposes major surgery within the past 4 weeks Participated in any other clinical study within the past 4 weeks Used murine biological products (except blinatumomab), unless it is proved no anti-mouse antibodies exist. Pregnancy or breast-feeding women Use of prohibited drugs: Steroids: Therapeutic doses of steroids must be stopped > 72 hours prior to CD19-CAR-T2 Cells infusion Allogeneic cellular therapy: Any donor lymphocyte infusions (DLI) must be completed > 4 weeks prior to CD19-CAR-T2 Cells infusion GVHD therapies: Any drug used for GVHD must be stopped > 4 weeks prior to CD19-CAR-T2 Cells infusion Chemotherapy: i. The following drugs must be stopped > 1 week prior to CTL019 infusion and should not be administered concomitantly or following lymphodepleting chemotherapy: hydroxyurea, vincristine, 6-mercaptopurine, 6-thioguanine, methotrexate <25 mg/m2, cytosine arabinoside < 10 mg/m2/day, asparaginase; ii. The following drugs must be stopped > 4 weeks prior to CTL019 infusion: salvage chemotherapy (e.g. clofarabine, cytosine arabinoside > 100 mg/m2, anthracyclines, cyclophosphamide), excluding the required lymphodepleting chemotherapy drugs Any situation that may increase the risk of the test or interfere with the test results

Ages Eligible for Study
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Minimum Age: 14 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: CD19-CAR-T2 T Cells<br>The subject's T cells will be modified to those which could identify and kill the tumor cells (CD19+ cells). These CD19-CAR-T2 T cells will be infused over 10-15 minutes on days Day 1, 2 and 3 tentatively according to the response to infusion. | Biological: CD19-CAR-T2 Cells<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The maximum tolerated dose(MTD) of CD19 positive relapsed/ refractory acute leukimia treated wtih CD19-CAR-T2 cells |  | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment | Adverse events and laboratory abnormalities (type, frequency and severity) | 12 months | 
| Overall Response Rate | Overall Response Rate (ORR), which includes Complete Remission (CR) and Complete Remission with Incomplete Blood Count Recovery (CRi), as determined by assessments of peripheral blood, bone marrow, CNS symptoms, physical exam (PE) and CSF. The primary endpoint will be based on the IRC assessment. The local investigator's assessed results will be used for sensitivity analysis. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Leukemia, CART CD19, Chemotherapy Resistant, Chemotherapy Refractory, CD19 +, Lymphoma