Relapse and refractory B cell malignancies Cancer Malignant neoplasms, B cell malignancy, B cell lymphoma, B cell leukaemia
Conditions
Interventions
Once a participant is enrolled, He/She will be assigned to a dose-specific group. Three dose levels will be evaluated and the infusion dose of CAR-T cells will start at low dose then rise to a higher
Sponsors
Gracell Biotechnologies Co., Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 2 to 70 years 2. Diagnosed with relapsed and refractory CD19+ B cell malignancies 3. Eastern cooperative oncology group (ECOG) performance status of 0 to 2 4. Life expectancy =12 weeks 5. Adequate organ function defined as: a. Serum ALT/AST =2.5 ULN b. Creatinine clearance (as estimated by Cockcroft Gault) =60 mL/min c. PT and APTT =1.5 ULN d. Total bilirubin =1.5 ULN e. Cardiac ejection fraction =45% f. No clinically significant ECG findings g. Baseline oxygen saturation >90% on room air 6. Agreement to the use of medical-approved-contraception during the period of trial and in 1 year after cell transfusion therapy 7. Quantifiable tumor burden 8. Informed consent given
Exclusion criteria
Exclusion criteria: 1. Have other tumors (except non-melanoma and cervical carcinoma in situ, bladder cancer, breast cancer that have a disease-free survival of more than 5 years) 2. Severe mental disorders 3. History of hereditary diseases including but not limited to: Fanconi anemia, Shut-Dai syndrome, Costman syndrome or any other known bone marrow failure syndrome 4. Grade 2-4 acute graft-versus-host disease (GVHD( (Glucksberg criteria) or extensive chronic GVHD (Seattle criteria) 5. Grade III-IV heart failure or myocardial infarction, angioplasty or stent placement, unstable angina pectoris, or other clinically prominent heart diseases within one year before enrollment; 6. History or presence of CNS disorder including but not limited to: seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement; 7. Positive for any of the following etiological tests: HIV, HBV, HCV, TPPA; 8. Presence of fungal, bacterial, viral, or other infection that is uncontrolled; 9. Severe allergies 10. History of autoimmune disease resulting in end-organ injury or requiring systemic immunosuppression/systemic disease-modifying agents within the last 2 years 11. History of pulmonary fibrosis 12. Involvement in other clinical trials = 4 weeks prior to enrollment 13. Presence of concomitant disease that requires systemic steroids or other immune suppressive therapy during the study period in the researcher's judgment 14. Patients who are contraindicated to cyclophosphamide, fludarabine, or melphalan 15. Allogeneic cell therapy (such as donor lymphocyte infusion, DLI) =6 weeks prior to enrollment 16. Poor adherence due to physical, family, social, geographic, and other factors, who cannot follow the research plan and follow-up plan 17. Pregnant and lactating women 18. Any other conditions that the researcher thinks it is inappropriate for the subject to anticipate the trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Presence of dose-limiting toxicity assessed by Common Terminology Criteria for Adverse Events (CTCAE v5.0) at 4 and 12 weeks following GC197 infusion 2. Overall response rate of patients who received GC197 infusion assessed by NCCN clinical practice guidelines in oncology: Acute Lymphoblastic Leukemia (2016.V2) for B-ALL response rate and Lugano 2014 for B-Lymphoma response rate at 24 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Clinical benefit of GC197 infusion measured by progression-free survival (PFS), overall survival (OS) and duration of remission (DOR) assessed at 4 and 12 weeks. 2. Response to GC197 infusion measured by changes in peripheral blood and bone marrow, CAR-T cell flow cytometry in peripheral blood, peripheral blood serum cytokines, lymphocyte subsets, and anti-GC197 antibody levels at -1, 4, 7, 10 and 14 days | — |
Countries
China
Contacts
Public ContactSanbin Wang
Outcome results
None listed