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

B-cell Acute Lymphoblastic Leukemia Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05639179
• Other study ID #: KM-010
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 5, 2022
• Est. completion date: December 31, 2025

Study information

• Verified date: December 2022
• Source: 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
• Contact: Wang Sanbin, Doctor
• Phone: 13187424131
• Email: Sanbin1011[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• B-ALL
• B-cell Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

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.

Locations

Country	Name	City	State
China	920th Hospital of Joint Logistics Support Force of People's Liberation Army of China	Kunming	Yunnan

Sponsors (1)

Lead Sponsor	Collaborator
920th Hospital of Joint Logistics Support Force of People's Liberation Army of China

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting toxicity (DLT)	Neurotoxicity and/or CRS=G3.	Up to 28 days after infusion
Primary	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 infusion
Secondary	Persistence of CAR-T cells	The persistence over time of CAR-T cells in the peripheral blood as determined by flow cytometry and qPCR.	Up to 24 weeks after infusion
Secondary	Objective response rate (ORR)	Patients who achieve CR(complete response) or CRi after infusion	At 4,8,12 weeks after infusion
Secondary	Progression-free survival (PFS)	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.	Up to 24 weeks after infusion
Secondary	Overall survival (OS)	Overall survival (OS) is the time from randomization to death from any cause.	Up to 24 weeks after infusion
Secondary	Duration of remission (DOR)	Duration of remission (DOR) is the time from the first detection of CR or PR to the discovery of PD.	Up to 24 weeks after infusion