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

NCT ID: NCT04094766

Last Updated: 2020-11-05

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-01
• Study Completion Date: 2020-08-30

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.

Conditions

Refractory B Acute Lymphoblastic Leukemia; Relapse B Acute Lymphoblastic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

BLLCAR-L10D treatment group

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.

Group Type: EXPERIMENTAL

Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy

Intervention Type: DRUG

Patients will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of CAR-T cells. After a pre-treatment lymphodepletion therapy, patients will receive the Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy by intravenous injection.

Interventions

Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy

Patients will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of CAR-T cells. After a pre-treatment lymphodepletion therapy, patients will receive the Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy by intravenous injection.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 14 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nanjing Legend Biotech Co.

INDUSTRY

Sponsor Role: collaborator

Second Affiliated Hospital of Xi'an Jiaotong University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Aili He, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Second Affiliated Hospital of Xi'an Jiaotong University

Locations

Second Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, China

Countries

China

Other Identifiers

XJTU-BLLCAR-L10D

Identifier Type: -

Identifier Source: org_study_id