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

NCT05571540 | Withdrawn Phase 1

• 1 other identifier: PBC049
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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).

Conditions

B-cell Acute Lymphoblastic Leukemia; B-ALL

Keywords

universal CAR-T; CD19

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicity (DLT)

  Neurotoxicity and/or CRS≥G3.

  Up to 28 days after LstCAR019 infusion

• Incidence of Treatment Related adverse events (AEs)

  The frequency, severity, and laboratory findings of all adverse events/serious adverse events are included.

  Up to 12 months after LstCAR019 infusion

Secondary Outcomes (5)

• Persistence of CAR-T cells

  Up to 24 weeks after infusion

• Objective response rate (ORR)

  At 4 ,8 , 12 weeks after infusion

• Progression-free survival (PFS)

  Up to 24 weeks after infusion

• Overall survival (OS)

  Up to 24 weeks after infusion

• Duration of remission (DOR)

  Up to 24 weeks after infusion

Study Arms (1)

U-CAR-T Cells (LstCAR019)

EXPERIMENTAL

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

Biological: U-CAR-T Cells (LstCAR019)

Interventions

U-CAR-T Cells (LstCAR019) 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.

U-CAR-T Cells (LstCAR019)

Eligibility Criteria

• Age: 2 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, aged 2-75 years;
• A definite diagnosis of relapsed/refractory B-ALL and a percentage of primitive/naive lymphocytes \>5% in bone marrow at baseline (flow cytometry);
• CD19 expression was positive in bone marrow or peripheral blood tumor cells;
• ECOG score 0-2 points;
• Expected survival time ≥3 months;
• Adequate liver, kidney, heart and lung function;
• Patients who have recovered from acute toxic effects of prior chemotherapy should be excluded from the trial at least one week apart;
• 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;
• Voluntarily sign the informed consent.

You may not qualify if:

• Presence of other concurrent active malignancy;
• People with severe mental disorders;
• 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;
• Acute GVHD of grade II-IV or extensive chronic GVHD;
• 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;
• 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;
• 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;
• 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;
• Patients with severe history of allergy or allergic constitution;
• 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;
• Had or is suffering from interstitial lung disease (e.g., pneumonia, pulmonary fibrosis);
• Had undergone other clinical trials in the 4 weeks prior to participating in this trial;
• Poor compliance due to physiological, family, social, geographical and other factors, unable to cooperate with the study protocol and follow-up plan;
• For patients contraindicated with cyclophosphamide and fludarabine chemotherapy;
• 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;

Sponsors & Collaborators

• Kunming Hope of Health Hospital: lead

Study Sites (1)

Kunming Hope of Health Hospital

Kunming, Yunnan, 650000, China

Location

MeSH Terms

Conditions

Burkitt Lymphoma

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Li Li, MD

  Kunming Hope of Health Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 4, 2022
• First Posted: October 7, 2022
• Study Start: October 1, 2022
• Primary Completion: January 31, 2024
• Study Completion: October 31, 2024
• Last Updated: November 30, 2022

Record last verified: 2022-11

Locations

CN (1)