Novel Anti-CD19 Universal CAR-T Cells for r/r CD19+ 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 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).

Study Overview

• Status: Recruiting
• Conditions: B-cell Acute Lymphoblastic Leukemia; B-ALL
• Intervention / Treatment: Biological: UCAR-T Cells

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.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Wang Sanbin, Doctor; Phone Number: +86 13187424131; Email: sanbin1011@163.com

Study Locations

• China
  • Yunnan
    • Kunming, Yunnan, China, 650000
      • Recruiting
      • 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
      • Contact: Chen Li; Phone Number: 0871 64774206

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Assigned Interventions; Subjects who meet the enrollment conditions will receive intravenous infusion of UCAR-T Cells after lymphodepletion.

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting toxicity (DLT)	Neurotoxicity and/or CRS≥G3.	Up to 28 days after 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 infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Objective response rate (ORR)	Patients who achieve CR(complete response) or CRi after infusion	At 4,8,12 weeks after infusion
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
Overall survival (OS)	Overall survival (OS) is the time from randomization to death from any cause.	Up to 24 weeks after infusion
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

Collaborators and Investigators

• Sponsor: 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
• Investigators: Principal Investigator: Wang Sanbin, Doctor, 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2022
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): December 31, 2025

Study Registration Dates

• First Submitted: November 25, 2022
• First Submitted That Met QC Criteria: November 25, 2022
• First Posted (Actual): December 6, 2022

Study Record Updates

• Last Update Posted (Estimate): December 8, 2022
• Last Update Submitted That Met QC Criteria: December 7, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: CD19; universal CAR-T(UCAR-T)
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
• Other Study ID Numbers: KM-010

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No