Refractory B Acute Lymphoblastic Leukemia, Relapse B Acute Lymphoblastic Leukemia
Conditions
Keywords
Chimeric Antigen Receptor T cells, CD19 and CD22
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.
Interventions
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.
Sponsors
Nanjing Legend Biotech Co.
Second Affiliated Hospital of Xi'an Jiaotong University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
14 Years to 60 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of treatment related adverse events | Day 1-100 days after injection | Assessed by CTCAE v4.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
Other
| Measure | Time frame |
|---|---|
| Copy numbers of CAR-T cells in patients | Day 1-5 years after injection |
Countries
China
Outcome results
None listed