Novel Anti-CD19 Universal CAR-T Cells for r/r CD19+ B-ALL
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Assigned Interventions Subjects who meet the enrollment conditions will receive intravenous infusion of UCAR-T Cells after lymphodepletion. |
Biological: UCAR-T Cells
UCAR-T Cellswill be administered by vein. The trial includes two portions. The first portion is a"3+3"dose 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 the"3+3"dose escalation study. Twelve subjects will get infusion of UCAR-T Cells at the best dose verified in the first portion.
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
- Objective response rate (ORR) [At 4,8,12 weeks after infusion]
Patients who achieve CR(complete response) or CRi after infusion
- 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.
- Overall survival (OS) [Up to 24 weeks after infusion]
Overall survival (OS) is the time from randomization to death from any cause.
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Male or female, aged 2-75 years;
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A definite diagnosis of relapsed/refractory B-ALL and a percentage of primitive/naive lymphocytes >5% in bone marrow at baseline (flow cytometry);
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CD19 expression was positive in bone marrow or peripheral blood tumor cells;
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ECOG score 0-2 points;
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Expected survival time ≥3 months;
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Adequate liver, kidney, heart and lung function;
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Patients who have recovered from acute toxic effects of prior chemotherapy should be excluded from the trial at least one week apart;
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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;
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Voluntarily sign the informed consent.
Exclusion Criteria:
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Presence of other concurrent active malignancy;
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People with severe mental disorders;
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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;
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Acute GVHD of grade II-IV or extensive chronic GVHD;
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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;
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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;
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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;
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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;
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Patients with severe history of allergy or allergic constitution;
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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;
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Had or is suffering from interstitial lung disease (e.g., pneumonia, pulmonary fibrosis);
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Had undergone other clinical trials in the 4 weeks prior to participating in this trial;
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Poor compliance due to physiological, family, social, geographical and other factors, unable to cooperate with the study protocol and follow-up plan;
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For patients contraindicated with cyclophosphamide and fludarabine chemotherapy;
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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;
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Receiving donor lymphocyte infusion within 6 weeks before enrollment;
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Pregnant and lactating women;
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Any other condition that the investigator deemed inappropriate for inclusion.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China | Kunming | Yunnan | China | 650000 |
Sponsors and Collaborators
- 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
Investigators
- Principal Investigator: Wang Sanbin, Doctor, 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- KM-010