Relapse and Refractory T cell acute lymphoblastic leukaemia (T-ALL), Relapse and Refractory T cell lymphoblastic lymphoma (T-LBL) Cancer Acute lymphoblastic leukaemia, lymphoblastic T-cell lymphoma
Conditions
Interventions
Enrolled participants are allocated to one of three different dose levels of GC027. The infusion dose of CAR-T cells will start at low dose and then rise to higher dose after completion of low dose gr
2. Dose level two: 1.8-3.6×10^7 cells/kg
3. Dose level three: 4-6×10^7 cells/kg.
Before CAR-T infusion, all participants will receive a preconditioning therapy suggested as: Fludarabine 30 mg/m^2×6d, Cyclophosphamide 300 mg/m^2×6d or Cyclop
Sponsors
Gracell Biotechnologies Co., Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 2 to 70 years 2. Diagnosed with relapsed and refractory CD7 + T cell acute lymphocytic leukemia (T-ALL) or relapsed and refractory CD7 + T lymphoblastic lymphoma (T-LBL) 3. Quantifiable tumor burden 4. Eastern cooperative oncology group (ECOG) performance status of 0 to 2 5. Life expectancy =12 weeks 6. 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 7. Recovered from acute toxic effects of prior chemotherapy =one week before entering this study 8. Agreement to use of medical-approved-contraception during the period of trial and in 1 year after cell transfusion therapy 9. Signed informed consent form
Exclusion criteria
Exclusion criteria: 1. Diagnosis of other malignancy (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 disease 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 or diagnosis of pulmonary fibrosis 12. Participation in other clinical trials =4 weeks prior to enrollment 13. Concomitant disease that require systemic steroids or other immune suppressive therapy during the study period in researcher's judgement 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 researcher think it is inappropriate for the subject to anticipate the trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Dose-limiting toxicity assessed by Common Terminology Criteria for Adverse Events (CTCAE v5.0) at 4 and 12 weeks following GC027 infusion 2. Percentage of participants with adverse events measured by Common Terminology Criteria for Adverse Events (CTCAE v5.0) at 4 and 12 weeks following GC027 infusion 3. Overall response rate of patients, determined by National Comprehensive Cancer Network (NCCN) clinical practice guidelines in oncology: Acute Lymphoblastic Leukemia (2016.V2) for T-ALL response rate and Lugano 2014 for T-LBL response rate, at 24 weeks following GC027 infusion | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Progression-free survival (PFS) determined from patient notes at 24 weeks following GC027 infusion 2. Overall survival (OS) determined from patient notes at 24 weeks 3. Duration of remission (DOR) determined from patient notes at 24 weeks 4. CD7 + T cells in peripheral blood at baseline (-1 days) and at 4, 7, 10, 14 days 5. CAR DNA copies measured by flow cytometry in peripheral blood and bone marrow at 4 and 12 weeks 6. CAR-T cell number measured by flow cytometry in peripheral blood and bone marrow at 4 and 12 weeks 7. Changes of peripheral blood serum cytokines measured by flow cytometry in peripheral blood and bone marrow at 4 and 12 weeks 8. Lymphocyte subsets measured by flow cytometry in peripheral blood and bone marrow at 4 and 12 weeks 9. Anti-GC027 antibody levels measured by flow cytometry in peripheral blood and bone marrow at 4 and 12 weeks | — |
Countries
China
Contacts
Public ContactSanbin Wang
Outcome results
None listed