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

NCT ID: NCT05571540

Last Updated: 2022-11-30

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-01
• Study Completion Date: 2024-10-31

Brief Summary

This is a single-arm, single-center, open-labeled clinical study to evaluate the safety and efficacy of LstCAR019 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 cells(LstCAR019) targeting CD19 for r/r B-ALL patients.

After enrollment, patients will get a 3-5 days lymphodepletion therapy, then the LstCAR019 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.

Conditions

B-cell Acute Lymphoblastic Leukemia; B-ALL

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

U-CAR-T Cells (LstCAR019)

Subjects who meet the enrollment conditions will receive intravenous infusion of U-CAR-T Cells (LstCAR019) after lymphodepletion.

Group Type: EXPERIMENTAL

U-CAR-T Cells (LstCAR019)

Intervention Type: BIOLOGICAL

LstCAR019 will 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 LstCAR019 at the best dose verified in the first portion.

Interventions

U-CAR-T Cells (LstCAR019)

LstCAR019 will 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 LstCAR019 at the best dose verified in the first portion.

Intervention Type: BIOLOGICAL

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 LstCAR019 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.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kunming Hope of Health Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Li Li, MD

Role: PRINCIPAL_INVESTIGATOR

Kunming Hope of Health Hospital

Locations

Kunming Hope of Health Hospital

Kunming, Yunnan, China

Countries

China

Other Identifiers

PBC049

Identifier Type: -

Identifier Source: org_study_id