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

Phase 2

Completed

• Conditions: B-Cell Acute Lymphoblastic Leukemia, Adult
• Interventions: Drug: CAR-T cells targeting CD19 and CD22

• Registration Number: NCT04788472
• Lead Sponsor: Zhejiang University

Brief Summary

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

Detailed Description

This study was designed as a prospective, open-label, single-center study. It aims to evaluate the efficacy and safety of CD19 CAR-T cells in combination with dasatinib for the treatment of newly diagnosed Ph-positive B-cell acute lymphoblastic leukemia in adult.

Study Timeline

• Study Start: 2021-03-05
• Study First Submitted: 2021-03-05
• Study First Submitted QC: 2021-03-05
• Study First Posted: 2021-03-09
• Primary Completion: 2024-08-31
• Study Completion: 2024-08-31
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-16
• Last Update Posted: 2024-10-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 28

Inclusion Criteria

1. Age ≥ 18 years old;
2. Subjects with a diagnosis of B-cell acute lymphoblastic leukemia according to the 2016 edition of the WHO classification criteria for acute leukemia;
3. Subjects whose chromosomal and fusion gene analysis showed positivity for the Ph chromosome, BCR/ABL1 fusion gene;
4. Leukemia cells were CD19 and CD22 positive;
5. Patients with newly diagnosed B-ALL were not treated with standard chemotherapy regimens;
6. Serum total bilirubin ≤ 51 mol/L, serum ALT and AST both ≤ 3 times the upper limit of the normal range, blood creatinine ≤ 176.8 mol/L;
7. Echocardiography showed a left ventricular ejection fraction (LVEF) ≥50%;
8. Subjects had no active pulmonary infection and oxygen saturation ≥92% without oxygen;
9. The prognosis for survival is more than 3 months;
10. ECOG score 0-2;
11. Subjects volunteered to participate in this trial and signed an informed consent form.

Exclusion Criteria

Subjects with any of the following exclusion criteria were not eligible for enrollment in this trial:

1. Those with a history of epilepsy or other central nervous system disorders;
2. Those with a history of prolonged QT period or severe cardiac disease;
3. Women who are pregnant or breastfeeding (the safety of this therapy for the unborn child is not known);
4. Those with uncontrolled active infection;
5. Active hepatitis B or hepatitis C virus infection;
6. Those who have previously used any gene therapy product;
7. Those with insufficient amplification (<5-fold) in response to CD3/CD28 co-stimulatory signals;
8. Creatinine > 2.5 mg/dl or ALT / AST > 3 times the upper limit of the normal range or bilirubin > 2.0 mg/dl;
9. Those who suffer from other uncontrolled medical conditions that, in the opinion of the investigator, make them unsuitable for enrollment;
10. HIV-infected persons;
11. Any condition that, in the opinion of the investigator, may increase the risk to the subject or interfere with the results of the test.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CAR-T therapy	CAR-T cells targeting CD19 and CD22	Administration of CD19 and CD22 CAR T-cells

Primary Outcome Measures

Name	Time	Method
Complete molecular response (CMR) rate	Up to 1 month after CAR-T cells infusion	Complete molecular response (CMR) rate after CD19 CAR-T cell therapy

Secondary Outcome Measures

Name	Time	Method
Complete molecular response (CMR) rate	Up to 1 month after CAR-T cells infusion	Complete molecular response (CMR) rate after CD22 CAR-T cell therapy
Leukemia-free survival (LFS)	Up to 2 years after CD19 CAR-T cells infusion	From the complete remission to the occurrence of any event, including death, relapse (any one occurs first), and the last visit
Overall survival (OS)	Up to 2 years after CD19 CAR-T cells infusion	From the first infusion of CD19 CAR-T cells to death or the last visit
cumulative incidence of relapse (CIR)	Up to 2 years after CD19 CAR-T cells infusion	From the complete remission to relapse
Incidence of treatment-emergent adverse events (TEAEs)	Through study completion, an average of 2 years	Incidence of treatment-emergent adverse events (Safety and Tolerability)
Characterization of relapse	Through study completion, an average of 2 years	Including expression of CD19, CD22 and mutations in the ABL1 gene

Trial Locations

Locations (1)

The First Affiliated Hospital, College of Medicine, Zhejiang University; 🇨🇳 Hangzhou, Zhejiang, China