Novel Anti-CD19 Universal CAR-T Cells for r/r CD19+ B-ALL

Trial Title: Novel Anti-CD19 Universal CAR-T Cells for r/r CD19+ B-ALL

NCT ID: NCT05639179

Condition: B-cell Acute Lymphoblastic Leukemia
B-ALL

Conditions: Official terms:
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid

Conditions: Keywords:
universal CAR-T(UCAR-T)
CD19

Study type: Interventional

Study phase: Phase 1/Phase 2

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Biological
Intervention name: UCAR-T Cells
Description: 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.
Arm group label: Assigned Interventions

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.

Criteria for eligibility:
Criteria:
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.

Gender: All

Minimum age: 2 Years

Maximum age: 75 Years

Healthy volunteers: No

Locations:

Facility:
Name: 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China

Address:
City: Kunming
Zip: 650000
Country: China

Status: Recruiting

Contact:
Last name: Chen Li

Phone: 64774206

Phone ext: 0871

Start date: December 5, 2022

Completion date: December 31, 2025

Lead sponsor:
Agency: 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
Agency class: Other

Source: 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05639179