Safety and Efficacy of Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy in R/R Acute B Lymphoblastic Leukemia

Study Overview
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Brief Summary
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This is a single arm, open-label, dose escalation clinical study to evaluate the safety and efficacy of infusion of dual specificity CD19 and CD22 CAR-T cells in patients with relapsed and refractory acute B lymphoblastic leukemia.

Detailed Description
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CD19-directed CAR-T cell therapy has shown promising results for the treatment of relapsed or refractory acute B lymphoblastic leukemia. CD19 and CD22 are proteins usually expressed on the surface of the B leukemia cells. The dual specificity CAR enables the T-cells to recognize and kill the tumor cell through recognition of CD19 and CD22.

Official Title
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A Phase I Clinical Study of Dual Specificity CD19 and CD22 Chimeric Antigen Receptor T Cell Therapy in Relapsed or Refractory Acute B Lymphoblastic Leukemia

Conditions
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Refractory B Acute Lymphoblastic Leukemia, Relapse B Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Drug: Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent could be acquired; Diagnosed with relapse/refractory acute lymphoblastic leukemia; Relapse was defined as recurrence of blast cell(more than 5%) in peripheral blood or in bone marrow or extramedullary involvement; Refractory was defined as failed to achieve complete remission after two courses of induction therapy; CD19/CD22 postive leukemia cell was confirmed by flow cytometry or immunohistochemistry within 90 days since enrollment in this trial; Karnofsky score ≥70; Results of pregnant test should be negative, and agree to conception control during treatment and 6 months after CAR-T infusion. Adequate organ function: EF≥50%; normal ECG; CCR ≥ 50ml/min or Cr < 2.0mg/dL or < 2 times upper limitation of normal; ALT and AST<5 times upper limitation of normal; Serum bilirubin ≤ 3.0mg/dL; DLCO or FEV1 > 45% of predict value; At least 2 weeks intervals since the last chemotherapy; At least 2 weeks intervals since the last anti-GVHD therapy if patients have ever ; Exclusion Criteria: Patients diagnosed with acute promyelocytic leukemia:t(15;17)(q22;q12); Women in pregnancy and lactation; Uncontrolled infection, Active HBV or HCV infection, HIV positive or any other deadly bacterial/virual diseases; Long term use of systemic corticosteroids(5mg per day for 2 weeks); Any other uncontrolled life-threaten diseases; Patients with history of anaphylaxis to any drugs; With central nervous system (CNS) involvement; Patients with GVHD after allo-HSCT who needed immunosuppressive agents ; Patients with acute autoimmune diseases such as psoriasis or rheumatoid arthritis; Other conditions that principle investigator considered may increase the risk of the patients or interference the results.

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 60 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: BLLCAR-L10D treatment group<br>In BLLCAR-L10D treatment group, patients will be treated with dual specificity CD19 and CD22 CAR-T cells with a escalation approach, 3 CAR-T dosage will be tested in this study: 0.5×10^6, 1.5×10^6, 2.0×10^6 CAR-T cells/kg. | Drug: Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy<br>* Patients will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of CAR-T cells. After a pre-treatment lymphodepletion therapy, patients will receive the Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy by intravenous injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of treatment related adverse events | Assessed by CTCAE v4.0 | Day 1-100 days after injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate | Objective response include complete remission and partial remission | Day 1-5 years after injection | 
| Overall survival |  | Day 1-5 years after injection | 
| Progression free survival |  | Day 1-5 years after injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chimeric Antigen Receptor T cells, CD19 and CD22