CD19CD22 CAR-T Therapy in Patients With High-Risk B Acute Lymphoblastic Leukemia (B-ALL).

Study Overview
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Brief Summary
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Clinical trial for the safety and efficacy of induction chemotherapy with VA regime and bridging CD19CD22 CAR-T therapy in adult patients with newly diagnosed high-risk and Ph- B-ALL

Detailed Description
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To evaluate the safety and efficacy of induction chemotherapy with VA regime and bridging CD19CD22 CAR-T therapy in Adult patients with newly diagnosed high-risk and Ph- B-ALL in this prospective, single arm study.

Official Title
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Clinical Trial for the Safety and Efficacy of Induction Chemotherapy With Azacitidine+Venetoclax (VA) and Bridging CD19CD22 CAR-T Therapy in Adult Patients With Newly Diagnosed High-Risk and Ph-negative (Ph-) B-ALL

Conditions
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B Acute Lymphoblastic Leukemia, Ph-Negative ALL, High Risk Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Drug: Azacitidine Injection
* Drug: Venetoclax
* Drug: CD19CD22 CAR-T


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age≥18 and ≤65 years old Newly diagnosed and high risk B-ALL according to the 2022 WHO classification The immunophenotype of leukemia cells were CD19 and CD22 positive and Ph-; Anticipated survival time more than 12 weeks; Those who voluntarily participated in this trial and provided informed consent. Exclusion Criteria: History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular hemorrhagic diseases; Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past; Pregnant (or lactating) women; Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis); Human immunodeficiency virus (HIV) positive; Active infection of hepatitis B virus or hepatitis C virus Previously treated with any CAR-T cell product or other genetically-modified T cell therapies; Creatinine>2.5mg/dl, or ALT / AST > 3 times of normal amounts, or bilirubin>2.0 mg/dl; Other uncontrolled diseases that were not suitable for this trial; Any situations that the investigator believes may increase the risk of patients or interfere with the results of study.

Ages Eligible for Study
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Minimum Age: 18 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: CAR-T therapy<br>Therapeutic outcomes in adults with Ph- B-ALL have substantially improved in the last decade, with complete remission (CR) and long-term overall survival (OS) rates of around 90% and 40%-50%, respectively. The presence of measurable residual disease (MRD) is the strongest predictor of relapse in B-ALL. In this study, high risk Ph- B-ALL patients receive the induction chemotherapy with Azacitidine+Venetoclax. After induction chemotherapy with Azacitidine+Venetoclax (VA regime), each subject receives CD19CD22 CAR-T cells by intravenous infusion. The patients with MRD negative will undergo HSCT. | Drug: Azacitidine Injection<br>* Azacitidine Injection 75mg/square meter/day, day1-7, subcutaneous injection<br>* Other names: Azacitidine;Drug: Venetoclax<br>* Venetoclax 100mg day 1, 200mg day 2, 400mg d3-d21, oral<br>* Other names: ABT-199;Drug: CD19CD22 CAR-T<br>* After induction chemotherapy with Azacitidine+Venetoclax, each subject receives CD19CD22 CAR-T cells by intravenous infusion<br>* Other names: GDC-0199;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Remission Rate | MRD Negative Remission Rate after CD19CD22 cell therapy | The cycle of CD19CD22 cell therapy is day 2-4; Effect evaluation was day 21 after CD19CD22 cells infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Remission Rate of VA regime | Complete Remission Rate after VA regime | The cycle of VA regime is day 21; Effect evaluation was day 7 after VA regime | 
| Complete Molecular Remission Rate | Complete Molecular Remission Rate after CD19CD22 CAR-T cell therapy | The cycle of CD19CD22 cell therapy is day 2-4; Effect evaluation was day 21 after CD19CD22 cells infusion | 
| Overall survival (OS) | From the first infusion of CD19CD22 cells to death or the last visit | The cycle of CD19CD22 cell therapy is day 2-4; Effect evaluation was 2 years after CD19CD22 CAR-T cells infusion | 
| Leukemia-free survival (LFS) | Up to 2 years after CD19CD22 CAR-T cells infusion | The cycle of CD19CD22 cell therapy is day 2-4; Effect evaluation was 2 years after CD19CD22 CAR-T cells infusion |