B-ALL, B-cell Acute Lymphoblastic Leukemia
Conditions
Keywords
universal CAR-T(UCAR-T), CD19
Brief summary
This is a single-arm, single-center, open-labeled clinical study to evaluate the safety and efficacy of UCAR-T Cells injection for patients with relapsed/refractory(r/r) B-cell Acute Lymphoblastic Leukemia(B-ALL).
Detailed description
Although the anti-CD19 CAR-T cell therapies have gained significant clinical outcome in patients with r/r B-ALL，autologous CAR-T is not feasible for some patients. To make further improvement, the investigators are going to conduct a clinical trial using universal CAR-T(UCAR-T) cells targeting CD19 for r/r B-ALL patients. After enrollment, patients will get a 3-5 days lymphodepletion therapy, then the UCAR-T Cells will be infused by vein. Subjects will be followed for safety and efficacy up to 12 weeks. For those with a durable remission 12 weeks after infusion, the follow-up will last for at least 12 months for disease control.
Interventions
BIOLOGICALUCAR-T Cells
UCAR-T Cellswill be administered by vein. The trial includes two portions. The first portion is a3+3dose escalation study, in which three dose groups are set:Dose level one:1×10\^6 cells/kg;Dose level two:2×10\^6 cells/kg;Dose level three:5×10\^6 cells/kg. Each dose group requires at least three subjects. The trial will start from dose level one. The second portion includes a dosage extended cohort and will start after the finish of the3+3dose escalation study. Twelve subjects will get infusion of UCAR-T Cells at the best dose verified in the first portion.
Sponsors
920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female, aged 2-75 years; 2. A definite diagnosis of relapsed/refractory B-ALL and a percentage of primitive/naive lymphocytes \>5% in bone marrow at baseline (flow cytometry); 3. CD19 expression was positive in bone marrow or peripheral blood tumor cells; 4. ECOG score 0-2 points; 5. Expected survival time ≥3 months; 6. Adequate liver, kidney, heart and lung function; 7. Patients who have recovered from acute toxic effects of prior chemotherapy should be excluded from the trial at least one week apart; 8. Women of childbearing age have negative blood pregnancy test before the start of the trial, and agree to take effective contraceptive measures during the trial until the last follow-up; male subjects with partners of childbearing potential agree to take effective contraceptive measures during the trial until the last follow-up; 9. Voluntarily sign the informed consent.
Exclusion criteria
1. Presence of other concurrent active malignancy; 2. People with severe mental disorders; 3. A history of any of the following genetic disorders, such as Fanconi anemia, Schu-Day syndrome, Gerstmann syndrome, or any other known bone marrow failure syndrome; 4. Acute GVHD of grade II-IV or extensive chronic GVHD; 5. Had grade III-IV heart failure or myocardial infarction, cardiac angioplasty or stenting, unstable angina pectoris, or other clinically prominent heart disease within one year prior to enrollment; 6. The presence of any indwelling catheter or drainage (e.g., percutaneous nephrostomy, indwelling catheter, bile drainage, or pleural/peritoneal/pericardial catheter), except for patients who are permitted to use dedicated central venous catheters; 7. A history or disease of the central nervous system(CNS), such as seizure disease, cerebrovascular ischemia/bleeding, dementia, cerebellar disease, or any autoimmune disease involving the CNS; 8. Human immunodeficiency virus (HIV) seropositivity; Hepatitis B surface antigen positive or hepatitis B core antibody positive, and HBV-DNA positive; Patients with hepatitis C (HCV-RNA quantitative test results positive); Or the presence of other serious active viral or bacterial infections or uncontrolled systemic fungal infections; 9. Patients with severe history of allergy or allergic constitution; 10. A history of autoimmune diseases (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus) leading to end-organ damage or requiring systemic immunosuppressive/systemic disease modulating drugs within the past 2 years; 11. Had or is suffering from interstitial lung disease (e.g., pneumonia, pulmonary fibrosis); 12. Had undergone other clinical trials in the 4 weeks prior to participating in this trial; 13. Poor compliance due to physiological, family, social, geographical and other factors, unable to cooperate with the study protocol and follow-up plan; 14. For patients contraindicated with cyclophosphamide and fludarabine chemotherapy; 15. Subjects requiring systemic corticosteroid therapy (prednisone ≥5mg/ day or equivalent dose of another corticosteroid) or other immunosuppressive agents within 1 month after UCAR-T cell reinfusion, except for adverse events; 16. Receiving donor lymphocyte infusion within 6 weeks before enrollment; 17. Pregnant and lactating women; 18. Any other condition that the investigator deemed inappropriate for inclusion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-limiting toxicity (DLT) | Up to 28 days after infusion | Neurotoxicity and/or CRS≥G3. |
| Incidence of Treatment Related adverse events (AEs) | Up to 12 months after infusion | The frequency, severity, and laboratory findings of all adverse events/serious adverse events are included. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | Up to 24 weeks after infusion | Progression-free survival (PFS) is the time between the time a patient with tumor disease receives treatment and the time between the observation of disease progression or death from any cause. |
| Persistence of CAR-T cells | Up to 24 weeks after infusion | The persistence over time of CAR-T cells in the peripheral blood as determined by flow cytometry and qPCR. |
| Duration of remission (DOR) | Up to 24 weeks after infusion | Duration of remission (DOR) is the time from the first detection of CR or PR to the discovery of PD. |
| Overall survival (OS) | Up to 24 weeks after infusion | Overall survival (OS) is the time from randomization to death from any cause. |
| Objective response rate (ORR) | At 4,8,12 weeks after infusion | Patients who achieve CR(complete response) or CRi after infusion |
Countries
China
Contacts
Primary ContactWang Sanbin, Doctor
Outcome results
None listed