Relapsed/refractory B-cell malignancies
Conditions
Interventions
Dose level 1 for patients with B-ALL:IV infusion of aCD19XCD22 bispecific CAR-T cells (CT120A) 0.5×10^6 CAR+ T cells/kg
Dose level 2 for patients with B-ALL:IV infusion of aCD19XCD22 bispecific CAR-T cells (CT120A) 1×10^6 CAR+ T cells/kg
Dose level 3 for patients with B-ALL:IV infusion of aCD19XCD22 bispecific CAR-T cells (CT120A) 2×10^6 CAR+ T cells/kg
Dose level 1 for patients with BCL:IV infusion of aCD19XCD22 bispecific CAR-T cells (CT120A) 1×10^6 CAR+ T cells/kg
Dose level 2 for patients with BCL:IV infusion of aCD19XCD22 bispecific CAR-T cells (CT120A) 2×10^6 CAR+ T cells/kg
Dose level 3 for patients with BCL:IV infusion of aCD19XCD22 bispecific CAR-T cells (CT120A) 3×10^6 CAR+ T cells/kg
Sponsors
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. Subjects with B-cell malignancies, BCL and B-ALL, that met the criteria from National Comprehensive Cancer Network (NCCN) guidelines for B-Cell Lymphomas (2020.V1) and Acute Lymphoblastic Leukemia (2018.V1). 2. One of the following requirements must be met for B-ALL prior to enrollment: (1) Refractory B-ALL that has failed to achieve CR after 2 lines of standard therapies; (2) Relapse of B-ALL after 2 lines or more of systemic therapies. 3. All of the following requirements must be met for B-ALL before enrollment: (1) Bone marrow with >=5% lymphoblasts; (2) Subjects with Ph+ ALL that are intolerant to more than two tyrosine kinase inhibitors or resistant to tyrosine kinase inhibitor therapy; however, subjects with Ph+ ALL who have T315i mutation or Ph- ALL are allowed; 4. Subjects with BCL must have failed at least 2 lines of therapies (one standard chemotherapy regimen + one salvage chemotherapy) or relapsed after treatments before enrollment. They must have received anti-CD20 monoclonal antibody (unless the investigator determines that tumor is CD20-negative) and anthracycline-containing standard chemotherapy regimens. Meanwhile, one of the following requirements must be met: (1) ineligible for autologous hematopoietic stem cell translation (auto-HSCT); (2) refusal to receive auto-HSCT; (3) relapsed after auto-HSCT; 5. According to Lugano response criteria 2014, at least one measurable tumor lesion with the longest diameter of = 1.5cm should be present; subjects with B-ALL do not need to meet this requirement; 6. Aged 18-70 years; both genders are allowed; 7. Positive expression of both CD19 and CD22 detected by immunohistochemistry in the bone marrow or peripheral blood or biopsy; results obtained within 60 days before signing informed consent form are acceptable if sampling is inappropriate at the time of screening. It can be determined by the investigator for enrollment on a case-by-case basis; 8. Expected life expectancy >=12 weeks; 9. Total serum bilirubin must be =30 ml/min/1.73m2; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =50%; blood oxygen saturation>= 95%; 12. Corticosteroids: treatment with corticosteroid therapy must be stopped at least 72 hours before CAR-T cell infusion; however, corticosteroids at a physiological dose (<12mg/m2/day of hydrocortisone or the equivalent) are allowed; 13. Absence of active lung infection; 14. No contraindications for leukapheresis; 15. After signing the informed consent form, subjects and their partners must be willing to use effective method of contraception, devices or medicines, within one year after CAR-T cell infusion; female participants of childbearing potential must have a negative pregnancy test in serum or urine during screening; 16. Subjects must be willing to participate in the study and sign the written informed consent form.
Exclusion criteria
Exclusion criteria: 1. History of allergy to any component in the cell therapy product; 2. Patients with ALL accelerated from chronic myeloid leukemia based on the classification of World Health Organization (WHO); 3. Isolated extramedullary disease in B-ALL; 4. Patients with acute graft-versus-host disease (GVHD) graded as Glucksberg grade II-IV or IBMTR Severity Index of B-D; patients with acute or chronic GVHD who require systemic therapies within 4 weeks before enrollment; 5. Treatment with a live vaccine within 4 weeks prior to enrollment; 6. History of allogeneic HSCT; 7. Subjects with central-nervous system (CNS) diseases (e.g., brain aneurysm, epilepsy, brain stroke, dementia, psychosis) that are unrelated to the involvement of B-cell malignancies. Whether to exclude CNS or gastrointestinal involvement of B-cell malignancies will be determined by the investigator; 8. Subjects with severe active infection except simple urinary tract infection and bacterial pharyngitis, or who are currently receiving IV antimicrobials for management, or have received IV antimicrobial treatment one week prior to cell infusion. However, prophylactic anti-bacterial, anti-viral and anti-fungal therapies are allowed; 9. Seropositive for hepatitis B antigen (HBsAg) or hepatitis B antibody (HBcAb) and hepatitis B virus (HBV) DNA > 100 IU/mL in the peripheral blood; 10. Seropositive for hepatitis C antibodies and hepatitis C virus (HCV) RNA in the peripheral blood; 11. Subjects with other acquired or innate immunodeficiency, including but not limited to being positive for Human Immunodeficiency Virus (HIV) antibody, CMV DNA or syphilis; 12. Subjects with class III/IV cardiovascular disability according to the New York Heart Association (NYHA) Classification; 13. History of other primary malignancies other than non-melanoma skin cancer such as basal cell carcinoma that have been cured by resection; disease-free carcinoma in situ (e.g., cervix, bladder, breast); other primary cancers with no relapse = 5 years after treatments; 14. Subjects with autoimmune diseases (e.g. Crohn disease, rheumatoid arthritis, systemic lupus erythematosus) that require systemic immunosuppressants in the past 2 years or are immune-incompetent; 15. Patients with other conditions adjudicated by the investigator as unsuitable for enrollment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum tolerated dose of CT120A cells;Dose-limiting toxicity of CT120A cells;Occurrence and severity of treatment-emergent adverse events (TEAEs); | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall response rate (ORR);Time to first response;Time to complete response (CR);Best overall response rate (BOR);Duration of response (DOR);Progression-free survival (PFS);Overall survival (OS); | — |
Countries
China
Contacts
Public ContactJianfeng Zhou
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Outcome results
None listed