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

Phase 2

Recruiting

• Conditions: B Acute Lymphoblastic Leukemia; Ph-Negative ALL; High Risk Acute Lymphoblastic Leukemia
• Interventions: Drug: Azacitidine Injection; Drug: Venetoclax; Drug: CD19CD22 CAR-T

• Registration Number: NCT06078306
• Lead Sponsor: The First Affiliated Hospital of Soochow University

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2023-09-11
• Status Verified: 2023-10
• Study First Submitted QC: 2023-10-05
• Study First Posted: 2023-10-11
• Last Update Submitted: 2024-04-19
• Study Start: 2024-04-20
• Last Update Posted: 2024-04-22
• Primary Completion: 2024-09-10
• Study Completion: 2025-09-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. Age≥18 and ≤65 years old
2. Newly diagnosed and high risk B-ALL according to the 2022 WHO classification
3. The immunophenotype of leukemia cells were CD19 and CD22 positive and Ph-;
4. Anticipated survival time more than 12 weeks;
5. Those who voluntarily participated in this trial and provided informed consent.

Exclusion Criteria

1. History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular hemorrhagic diseases;
2. Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;
3. Pregnant (or lactating) women;
4. Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis);
5. Human immunodeficiency virus (HIV) positive; Active infection of hepatitis B virus or hepatitis C virus
6. Previously treated with any CAR-T cell product or other genetically-modified T cell therapies;
7. Creatinine>2.5mg/dl, or ALT / AST > 3 times of normal amounts, or bilirubin>2.0 mg/dl;
8. Other uncontrolled diseases that were not suitable for this trial;
9. Any situations that the investigator believes may increase the risk of patients or interfere with the results of study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CAR-T therapy	Azacitidine Injection	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.
CAR-T therapy	CD19CD22 CAR-T	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.
CAR-T therapy	Venetoclax	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.

Primary Outcome Measures

Name	Time	Method
Complete Remission Rate	The cycle of CD19CD22 cell therapy is day 2-4; Effect evaluation was day 21 after CD19CD22 cells infusion	MRD Negative Remission Rate after CD19CD22 cell therapy

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Xiaowen Tang; 🇨🇳 Suzhou, Jiangsu, China