Universal CAR-T Cell Therapy for Relapsed B-ALL

An Investigator-initiated Trial to Evaluate the Efficacy and Safety of Anti-CD19 Universal CAR-T Cells in the Treatment of Relapsed/Refractory(r/r) CD19+ B-cell Acute Lymphoblastic Leukemia(B-ALL)

This study is testing a new type of CAR-T cell therapy to see if it can help people with relapsed or hard-to-treat B-cell leukemia feel better and have more treatment options.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 2 Years to 75 Years
• Sex: All
• Sponsor: 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China (Academic / other)
• Drugs / interventions: chemotherapy, cyclophosphamide, fludarabine, prednisone, CAR-T
• Locations: 1 site (Kunming, Yunnan)
• Trial ID: NCT05639179 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of universal CAR-T (UCAR-T) cells targeting CD19 in patients with relapsed or refractory B-cell Acute Lymphoblastic Leukemia (B-ALL). Participants will undergo a 3-5 day lymphodepletion therapy followed by infusion of UCAR-T cells. The study is designed as a single-arm, open-label trial, with follow-up assessments for safety and efficacy lasting up to 12 weeks, and extended follow-up for those achieving durable remission. The goal is to improve treatment options for patients who cannot receive autologous CAR-T therapy.

Who should consider this trial

Good fit: Ideal candidates are males and females aged 2-75 years with a confirmed diagnosis of relapsed/refractory B-ALL and positive CD19 expression.

Not a fit: Patients with concurrent active malignancies or those who have not recovered from the acute toxic effects of prior chemotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for patients with relapsed or refractory B-ALL who are not candidates for traditional CAR-T therapies.

How similar studies have performed: While anti-CD19 CAR-T therapies have shown success, the use of universal CAR-T cells is a novel approach that has not been extensively tested in this context.

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.

Where this trial is running

Kunming, Yunnan

• 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China — Kunming, Yunnan, China (Recruiting)

Study contacts

• Principal investigator: Wang Sanbin, Doctor — 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
• Study coordinator: Wang Sanbin, Doctor

Conditions B-cell Acute Lymphoblastic Leukemia; B-ALL; universal CAR-T; CD19