CD19-positive recurrent and refractory B cell malignancies Cancer
Conditions
Interventions
Biologic: Autologous CD19-specific chimeric antigen receptor (CAR)-T cells or allogeneic CD19 CAR-T cells from prior HLA-matched stem cell transplant donor
Other agents: Fludarabine, Cyclophosphamide
Sponsors
Siriraj Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. Adult patients with CD19-positive recurrent and refractory B cell malignancies, aged 18-70 years old 2. Karnofsky Performance Status (KPS) score =60, expected survival =3 months 3. Platelet count (PLT) =30 × 10^9/L 4. Lymphocyte count (LYM) =0.15 × 10^9/L 5. Serum alanine aminotransferase (ALT) =100 U/mL 6. Total bilirubin (T-BIL) =30 µmol/L 7. Creatinine =200 µmol/L 8. Women of childbearing age are negative for the urine pregnancy test before the start of dosing and agree to take effective contraceptive measures 9. Voluntary participation, good compliance: willing to take part in studies and cooperate with clinical observations and follow-up plan
Exclusion criteria
Exclusion criteria: 1. Clinically diagnosed as central nervous system leukemia 2. Patients with hyperleukocytosis (WBC =50 × 10^9/L), or the researcher judges that the patient cannot receive a complete treatment cycle due to his rapid disease progress 3. Patients with fungi, bacteria, viruses or other uncontrolled infections or requiring isolation 4. Patients with positive HIV, HBV, and HCV 5. Patients with central nervous system diseases such as stroke, epilepsy, dementia or autoimmune neurological disorders 6. Patients with myocardial infection, cardiac angiography or stent, active angina or other obvious clinical symptoms, or with cardiac asthma or cardiovascular lymphocytic infiltration within 12 months prior to enrollment 7. Patients who are receiving anticoagulant therapy or who have severe coagulation disorders (aPTT >70) 8. Patients who receive medication that may affect the safety and efficacy of CAR-T cell product 9. Patients with a history of allergies to the biologics used in this project 10. Pregnant or lactating women 11. Patients who use systemic steroids within 2 weeks prior to treatment (except for inhaled steroids) 12. Patients with other uncontrolled diseases who are considered to be unsuitable to anticipate in the research by researchers 13. Any conditions that researchers believe may increase the risk to patient safety or may interfere with the overall outcome
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Proportion of products successfully manufactured meeting the established release criteria with a goal of at least 1 million cells/kg at the end of culture, which typically takes 12 days, measured using recorded data about the combinations of the following metrics at the end of the manufacturing process: - Identity and quantity: immunophenotyping, cell counting, viability - Purity: immunophenotyping - Sterility: USP, blood culture system - Safety: replication-competent lentivirus (RCL), vector copy number (VCN), mycoplasma, endotoxin - Potency: CAR expression, cytotoxicity towards target tumor cells, cytokine production 2. Incidence and severity of adverse events and dose-limiting toxicity (DLT) measured using physical and neurologic examination and routine labs at baseline, days 1–8 (daily), day 14, day 21, and 1, 3, 6, and 12 months post-infusion. The National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 and ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells 2019 will be applied. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Complete response (CR) rate measured using data recorded in medical records at 1, 3, and 6 months post-infusion For B-cell lymphoma, the Lugano response criteria for non-Hodgkin lymphoma will be used. CR is defined as the complete disappearance of all detectable clinical evidence of disease, and disease-related symptoms if present prior to the therapy. For B-acute lymphoblastic leukemia (B-ALL), the criteria are based upon the NCCN guidelines version 4.2023 acute lymphoblastic leukemia. Definition of CR is as follows: - No circulating lymphoblasts or extramedullary disease: no lymphadenopathy, splenomegaly, skin/gum infiltration, testicular mass, CNS involvement - Trilineage hematopoiesis (TLH) and < 5% blasts - Absolute neutrophil count (ANC) = 1000/µL - Platelets =100,000/µL 2. MRD status measured using flow cytometry for B-ALL MRD at 1 month post-infusion. Not available for lymphoma. 3. Overall and event-free survival measured using the definition from the National Cancer Institute (NCI) at 1 year - Overall survival (OS) is the length of time from either the date of diagnosis or the start of treatment for a disease, such as cancer, that patients diagnosed with the disease are still alive. - Relapse-free survival (RFS) is the length of time after primary treatment for a cancer ends that the patient survives without any signs or symptoms of that cancer. 4. Amount of SiCF-019 in blood measured using antigen-based detection by flow cytometry at days 0, 7, 14, 21 and 1, 3, 6, and 12 months post-infusion | — |
Countries
Thailand
Contacts
Public ContactSudjit Luanpitpong
Outcome results
None listed