Safety and Efficacy of Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy in R/R Acute B Lymphoblastic Leukemia

Phase 1

Withdrawn

• Conditions: Refractory B Acute Lymphoblastic Leukemia; Relapse B Acute Lymphoblastic Leukemia
• Interventions: Drug: Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy

• Registration Number: NCT04094766
• Lead Sponsor: Second Affiliated Hospital of Xi'an Jiaotong University

Brief Summary

This is a single arm, open-label, dose escalation clinical study to evaluate the safety and efficacy of infusion of dual specificity CD19 and CD22 CAR-T cells in patients with relapsed and refractory acute B lymphoblastic leukemia.

Detailed Description

CD19-directed CAR-T cell therapy has shown promising results for the treatment of relapsed or refractory acute B lymphoblastic leukemia. CD19 and CD22 are proteins usually expressed on the surface of the B leukemia cells. The dual specificity CAR enables the T-cells to recognize and kill the tumor cell through recognition of CD19 and CD22.

Study Timeline

• Study Start: 2017-08-01
• Study First Submitted: 2019-09-17
• Study First Submitted QC: 2019-09-17
• Study First Posted: 2019-09-19
• Primary Completion: 2020-08-30
• Study Completion: 2020-08-30
• Status Verified: 2020-11
• Last Update Submitted: 2020-11-03
• Last Update Posted: 2020-11-05

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Written informed consent could be acquired;
2. Diagnosed with relapse/refractory acute lymphoblastic leukemia;
3. Relapse was defined as recurrence of blast cell(more than 5%) in peripheral blood or in bone marrow or extramedullary involvement;
4. Refractory was defined as failed to achieve complete remission after two courses of induction therapy;
5. CD19/CD22 postive leukemia cell was confirmed by flow cytometry or immunohistochemistry within 90 days since enrollment in this trial;
6. Karnofsky score ≥70;
7. Results of pregnant test should be negative, and agree to conception control during treatment and 6 months after CAR-T infusion.
8. Adequate organ function: EF≥50%; normal ECG; CCR ≥ 50ml/min or Cr < 2.0mg/dL or < 2 times upper limitation of normal; ALT and AST<5 times upper limitation of normal; Serum bilirubin ≤ 3.0mg/dL; DLCO or FEV1 > 45% of predict value;
9. At least 2 weeks intervals since the last chemotherapy;
10. At least 2 weeks intervals since the last anti-GVHD therapy if patients have ever ;

Exclusion Criteria

1. Patients diagnosed with acute promyelocytic leukemia:t(15;17)(q22;q12);
2. Women in pregnancy and lactation;
3. Uncontrolled infection, Active HBV or HCV infection, HIV positive or any other deadly bacterial/virual diseases;
4. Long term use of systemic corticosteroids(5mg per day for 2 weeks);
5. Any other uncontrolled life-threaten diseases;
6. Patients with history of anaphylaxis to any drugs;
7. With central nervous system (CNS) involvement;
8. Patients with GVHD after allo-HSCT who needed immunosuppressive agents ;
9. Patients with acute autoimmune diseases such as psoriasis or rheumatoid arthritis;
10. Other conditions that principle investigator considered may increase the risk of the patients or interference the results.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
BLLCAR-L10D treatment group	Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy	In BLLCAR-L10D treatment group, patients will be treated with dual specificity CD19 and CD22 CAR-T cells with a escalation approach, 3 CAR-T dosage will be tested in this study: 0.5×10\^6, 1.5×10\^6, 2.0×10\^6 CAR-T cells/kg.

Primary Outcome Measures

Name	Time	Method
Occurrence of treatment related adverse events	Day 1-100 days after injection	Assessed by CTCAE v4.0

Secondary Outcome Measures

Name	Time	Method
Objective response rate	Day 1-5 years after injection	Objective response include complete remission and partial remission
Overall survival	Day 1-5 years after injection
Progression free survival	Day 1-5 years after injection

Trial Locations

Locations (1)

Second Affiliated Hospital of Xi'an Jiaotong University; 🇨🇳 Xi'an, Shaanxi, China