Sequential CD19 and CD22 CAR-T Therapy for Newly Diagnosed Ph- B-ALL

Study Overview
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Brief Summary
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Clinical Trial for the Safety and Efficacy of Sequential CD19 and CD22 CAR-T Therapy for Adult Patients With Newly Diagnosed Ph Chromosome Negative B-cell Acute Lymphoblastic Leukemia

Detailed Description
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This is a prospective, single arm study. To evaluate the safety and efficacy of sequential CD19 and CD22 CAR-T cells in the treatment of adult newly diagnosed Ph chromosome negative B-cell acute lymphoblastic leukemia. The main endpoints were dose limiting toxicity (DLT) and incidence of adverse events (TEAEs).

Official Title
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Clinical Trial for the Safety and Efficacy of Sequential CD19 and CD22 CAR-T Therapy for Adult Patients With Newly Diagnosed Ph Chromosome Negative B-cell Acute Lymphoblastic Leukemia

Conditions
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B-Cell Acute Lymphoblastic Leukemia, Adult

Intervention / Treatment
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* Drug: CAR-T cells targeting CD19 and CD22


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age≥15 years old Newly diagnosed B-cell acute lymphoblastic leukemia according to the 2016 WHO classification The immunophenotype of leukemia cells were CD19 and CD22 positive Ph- or Ph- like negative 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); Active infection of hepatitis B virus or hepatitis C virus; Concurrent therapy with systemic steroids within 2 weeks prior to screening, except for the patients recently or currently receiving inhaled steroids; 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; Patients with HIV infection; 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: 15 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>Administration of CD19 and CD22 CAR T-cells | Drug: CAR-T cells targeting CD19 and CD22<br>* Each subject receives sequential CD19 and CD22 CAR-T cells by intravenous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity (DLT) | Adverse events assessed according to NCI-CTCAE v5.0 criteria | Baseline up to 28 days after CAR-T cells infusion | 
| Incidence of treatment-emergent adverse events (TEAEs) | Incidence of treatment-emergent adverse events [Safety and Tolerability] | Up to 2 years after CAR-T cells infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Remission Rate | Complete Remission Rate after CAR-T cell therapy | up to 28 days after CAR-T cells infusion | 
| Overall survival (OS) | From the first infusion of CD19 CAR-T cells to death or the last visit | Up to 2 years after CD19 CAR-T cells infusion | 
| Leukemia-free survival (LFS) | From the complete remission to the occurrence of any event, including death, relapse (any one occurs first), and the last visit | Up to 2 years after CD19 CAR-T cells infusion | 
| Quality of life | Assessment using European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) scale [For item1-28: max score: 112, min score: 28, higher scores mean a better outcome; for item 28-29: max score: 14, min score: 2, higher scores mean a worse outcome] to measure Quality of life at Baseline, Month 1, 3, 6, 9 and 12 | At Baseline, Month 1, 3, 6, 9 and 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CD19 CAR-T, CD22 CAR-T, Ph Chromosome Negative, B-ALL, Newly diagnosed