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

Refractory B Acute Lymphoblastic Leukemia Clinical Trial

Official title:

A Phase I Clinical Study of Dual Specificity CD19 and CD22 Chimeric Antigen Receptor T Cell Therapy in Relapsed or Refractory Acute B Lymphoblastic Leukemia

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04094766
• Other study ID #: XJTU-BLLCAR-L10D
• Status: Withdrawn
• Phase: Phase 1
• Start date: August 1, 2017
• Est. completion date: August 30, 2020

Study information

• Verified date: November 2020
• Source: Second Affiliated Hospital of Xi'an Jiaotong University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: August 30, 2020
• Est. primary completion date: August 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Refractory B Acute Lymphoblastic Leukemia
• Relapse B Acute Lymphoblastic Leukemia

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
China	Second Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shaanxi

Sponsors (2)

Lead Sponsor	Collaborator
Second Affiliated Hospital of Xi'an Jiaotong University	Nanjing Legend Biotech Co.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Copy numbers of CAR-T cells in patients		Day 1-5 years after injection
Primary	Occurrence of treatment related adverse events	Assessed by CTCAE v4.0	Day 1-100 days after injection
Secondary	Objective response rate	Objective response include complete remission and partial remission	Day 1-5 years after injection
Secondary	Overall survival		Day 1-5 years after injection
Secondary	Progression free survival		Day 1-5 years after injection