Relapsed/Refractory Malignant Hematological Tumors
Conditions
Interventions
Experimental group:A novel CAR-T cell injection co - expressing IL - 15
Sponsors
Tianjin Cancer Hospital Airport Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: All subjects must meet all of the following criteria: 1. With the consent of the person and signed the informed consent form, willing and able to comply with the planned visits, research treatment, laboratory tests and other trial procedures; 2. Patients with relapsed/refractory malignant hematological tumors diagnosed by clinical diagnosis; 3. Age >=18 years old, both male and female; 4. Subjects with an Eastern Cooperative Oncology Group (ECOG) score of 0~3 points; 5. The expected survival period is greater than 3 months from the date of signing the informed consent form; 6. HGB>=60g/L (blood transfusion is available); 7. Liver and kidney function, cardiopulmonary function meet the following requirements: a) Creatinine =50%; c) Blood oxygen saturation > 90%; d) Total bilirubin <=1.5×ULN; ALT and AST<=2.5×ULN; 8. If tumor cells are detected in peripheral blood during enrollment screening, the immunophenotype on the surface of tumor cells must be detected by flow cytometry: CD3/CD4/CD8 Any two of the three items are negative at the same time or peripheral blood tumor burden <=1%; 9. Subjects with pregnancy plans must agree to use contraception before enrollment in the study and after the study lasts for six months; The investigator should be notified immediately if the subject is pregnant or suspects pregnancy. Subjects in different cohorts still need to meet the following conditions: 1. Target CD19 cohort Mature B-cell lymphoma 1) Confirmed CD19 B-cell lymphoma by pathological and histological examination; i. Indolent B-cell lymphoma (CLL, FL, MZL, LPL, HCL); ii. Aggressive B-cell lymphoma (DLBCL, BL, MCL). 2) Meet the following criteria for relapsed or refractory B-cell lymphoma (meet 1 of the first 2 plus 3 of the following): 1. After 4 courses of standard chemotherapy, the tumor shrinks by less than 50% or the disease progresses; 2. Recurrence after achieving CR after standard chemotherapy; 3. Subjects must have received adequate prior therapy, including, at least: a) anti-CD20 monoclonal antibody; b) Combination chemotherapy with anthracyclines. Acute B lymphoblastic leukemia/B lymphoblastic lymphoma 1) Confirmed diagnosis of CD19 refractory/relapsed B lymphocytic leukemia by immunohistochemistry or flow cytometry. 2) Refractory/relapsed B lymphocytic leukemia (1 of the following 4 items is sufficient): i. Relapse within 6 months of first remission; ii. Primary refractory treatment that does not achieve complete remission within 2 cycles of standard chemotherapy regimen; iii. Complete remission or relapse has not been achieved after first-line or multi-line salvage chemotherapy; iv. Not suitable for hematopoietic stem cell transplantation conditions or who have abandoned hematopoietic stem cell transplantation due to conditional limitations or who have relapsed after hematopoietic stem cell transplantation. 2. Target CD19&CD20 cohort Mature B-cell lymphoma 1) Confirmed diagnosis of CD19 and/or CD20 B-cell lymphoma by pathological and histological examination; i. Indolent B-cell lymphoma (CLL, FL, MZL, LPL, HCL); ii. Aggressive B-cell lymphoma (DLBCL, BL, MCL). 2) Meet the following criteria for relapsed or refractory B-cell lymphoma (meet 1 of the first 2 plus 3 of the following): 1. After 4 courses of standard chemotherapy, the tumor shrinks by less than 50% or the disease progresses; 2. Recurrence after achieving CR after standard chemotherapy; 3. Subjects must have received adequ
Exclusion criteria
Exclusion criteria: If any of the following criteria are met, the subject cannot be enrolled: 1. Suffered from heart failure of New York Heart Association (NYHA) class > III, myocardial infarction, cardiac angioplasty or stent implantation, unstable angina pectoris, or other cardiac diseases with prominent clinical symptoms within one year before signing the informed consent form, or had a QTC interval > 480 ms at screening (the QTC interval is calculated using the Fridericia formula); 2. Has active GVHD or requires the use of immunosuppressive agents; 3. Had other malignancies within 5 years before screening, except for fully treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, locally prostate cancer after radical resection, and ductal carcinoma in situ of the breast after radical resection; 4. Had active or uncontrollable infections that required systemic treatment within 7 days before screening (excluding mild genitourinary tract infections and upper respiratory tract infections); 5. At screening, if the hepatitis B surface antigen (HBSAg) or hepatitis B core antibody (HbCAb) is positive and the peripheral blood hepatitis B virus (HBV) DNA is above the lower limit of detection, the subject should be excluded; if the hepatitis C virus (HCV) antibody is positive and the peripheral blood (HCV) RNA is positive, the subject should be excluded; those with positive (HIV) antibody; those with positive detection of cytomegalovirus (CMV) DNA; those with positive detection of Treponema pallidum specific antibody (TPPA) should be excluded; 6. Participated in other clinical trials within 4 weeks before signing the informed consent form, or the date of signing the informed consent form is within 5 half - lives of the last administration of the previous drug clinical trial (whichever is longer); 7. Has a history of severe allergy to biological products; 8. Has unstable systemic diseases as judged by the investigator: including but not limited to severe liver, kidney, or metabolic diseases that require drug treatment; 9. Pregnant or lactating women, and female subjects who plan to become pregnant within 2 years after cell infusion, or male subjects whose partners plan to become pregnant within 2 years after their cell infusion; 10. Situations that the investigator believes may increase the risk to the subject or interfere with the test results.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Security indicators; | — |
Secondary
| Measure | Time frame |
|---|---|
| Efficacy indicators;Cell metabolic kinetic indicators; | — |
Countries
China
Contacts
Public ContactYafei Wang
Tianjin Cancer Hospital Airport Hospital
Outcome results
None listed