Safety and Efficacy Study of CD22 CAR-T Cells for Relapsed or Refractory Acute Lymphoblastic Leukemia

Study Overview
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Brief Summary
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This is an open, single-arm, clinical study to evaluate efficacy and safety of anti CD22 CAR-T cell in the treatment of recurrent or refractory B-ALL

Detailed Description
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The CARs consist of an anti-CD22 single-chain variable fragment（scFv）, a portion of the human CD137（4-1BB） molecule, and the intracellular component of the human CD3ζ molecule. Prior to CAR-T cell infusion, the patients will be subjected to preconditioning treatment. After CAR-T cell infusion, the patients will be evaluated for adverse reactions and efficacy. The Main research objectives: To evaluate the safety and efficacy of CD22CAR-T in patients with recurrent or refractory B-ALL The Secondary research objectives: To investigate the cytokinetic characteristics of CD22CAR-T in patients with recurrent or refractory B-ALL

Official Title
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Safety and Efficacy Study of CD22 CAR-T Cells for Relapsed or Refractory Acute Lymphoblastic Leukemia

Conditions
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B-ALL

Intervention / Treatment
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* Biological: CD22 CAR-T


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with relapsed and refractory acute B-lymphoblastic leukemia who have any of the following: B-ALL patients with relapse (including bone marrow morphological relapse 1 and minimal residual relapse 2) after remission by chemotherapy or autologous stem cell transplantation; Primary B-ALL patients who can not be completely relieved by more than two times of repeated chemotherapy; High risk primary B-ALL patients who have not been relieved but are not suitable for re intensive therapy after 1-2 times of chemotherapy; Flow cytometry (FCM) showed CD 22 positive in bone marrow or peripheral blood; There should be at least one assessable lesion in B-ALL patients with simple extramedullary recurrence; The activity state score of the Eastern Cooperative Oncology Group (ECOG) was less than or equal to 2; The estimated survival time is more than 3 months; Need to sign informed consent. Exclusion Criteria: Serious cardiac insufficiency； Has a history of severe pulmonary function damaging; Other malignant tumors; Serious infection or persistent infection and can not be effectively controlled； Merging severe autoimmune diseases or immunodeficiency disease; Patients with active hepatitis (HBV DNA or HCV RNA positive); Patients with HIV infection or syphilis infection; Has a history of serious allergies on Biological products (including antibiotics); Being pregnant and lactating or having pregnancy within 12 months; Any situations that the researchers believe will increase the risks for the subject or affect the results of the study（including a history of serious mental illness, substance abuse and addiction）

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 70 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: CD22 CAR-T<br>Patients will be treated with CD22 CAR-T cells | Biological: CD22 CAR-T<br>* Biological: CD22 CAR-T; Drug: Cyclophosphamide,Fludarabine; Procedure: Leukapheresis<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Incidence and severity of adverse events | To evaluate the possible adverse events occurred within first one month after CD22 CAR-T infusion, including the incidence and severity of symptoms such as cytokine release syndrome and neurotoxicity | First month post CAR-T cells infusion | 
| Efficacy: Remission Rate | Remission Rate including complete remission(CR)、CR with incomplete blood count recovery(CRi)、No remission(NR) | 3 months post CAR-T cells infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy:duration of response (DOR) | duration of response (DOR) | 24 months post CAR-T cells infusion | 
| Efficacy: progression-free survival (PFS) | progression-free survival (PFS) time | 24 months post CAR-T cells infusion | 
| CAR-T proliferation | the copy number of CD19 CAR- T cells in the genomes of PBMC by qPCR method and percentage of CD19 CAR- T cells measured by flow cytometry method | 3 months post CAR-T cells infusion | 
| Cytokine release | Cytokine( IL-6,IL-10,IFN-γ,TNF-α ) concentration (pg/mL) by flow cytometry method | First month post CAR-T cells infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CD22 CAR-T， B-ALL