Clinical trial NCT04094766: Safety and Efficacy of Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy in R/R Acute B Lymphoblastic Leukemia
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Refractory B Acute Lymphoblastic Leukemia
Relapse B Acute Lymphoblastic Leukemia
Keywords: Chimeric Antigen Receptor T cells
CD19 and CD22
Lead sponsor: Second Affiliated Hospital of Xi'an Jiaotong University
Sponsor class: OTHER
Collaborators: name: Nanjing Legend Biotech Co.
First posted: 2019-09-19
Enrollment: 0
Sex: ALL
Minimum age (years): 14
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Occurrence of treatment related adverse events
timeFrame: Day 1-100 days after injection
Secondary outcomes:
measure: Objective response rate
timeFrame: Day 1-5 years after injection
measure: Overall survival
timeFrame: Day 1-5 years after injection
measure: Progression free survival
timeFrame: Day 1-5 years after injection
Other outcomes:
measure: Copy numbers of CAR-T cells in patients
timeFrame: Day 1-5 years after injection
Locations:
city: Xi'an
country: China
facility: Second Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
Study officials:
affiliation: Second Affiliated Hospital of Xi'an Jiaotong University
name: Aili He, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: