Modified CD19 CAR-T in Patients With Relapsed or Refractory CD19+ B-cell Malignancies

Phase 1

Recruiting

• Conditions: Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Leukemia
• Interventions: Biological: Modified anti-CD19 CAR T cells

• Registration Number: NCT04684472
• Lead Sponsor: Liqun Zou

Brief Summary

This study aims to evaluate the safety and tolerance of modified CD19 CAR T cells in treating refractory/relapsed B-cell malignancies. CAR-T cells will be investigated as a single agent both in relapsed/refractory B-cell acute lymphoblastic leukaemia (B-ALL) and up to 60% of patients with B-cell non-Hodgkin's lymphoma (NHL).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-12-21
• Study First Submitted QC: 2020-12-21
• Study First Posted: 2020-12-24
• Study Start: 2021-03-17
• Status Verified: 2022-09
• Last Update Submitted: 2022-09-22
• Last Update Posted: 2022-09-26
• Primary Completion: 2023-01-01
• Study Completion: 2024-01-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

1. Male or female aged 18-70 years;

2. Estimated survival time ≥ 12 weeks;

3. Histologically confirmed diagnosis of CD19+ B-ALL or CD19+ B-NHL(meeting one of the following conditions):

   1. Ineffectively or relapses after 2 or more remedial treatments
   2. Relapse after auto-HSCT or unsuitable for auto-HSCT;

4. At least one assessable tumor lesion;

5. ECOG performance status 0 to 2;

6. Creatinine clearance rate≥ 60 ml/min, ALT and AST ≤ 2.5 times of upper limit of normal, total bilirubin ≤ 1.5 times of upper limit of normal;

7. Male and female of reproductive potential must agree to use birth control during the study and for at least 30 days post study;

8. Patients or their legal guardians volunteer to participate in the study and sign the informed consent.

Exclusion Criteria

1. Patients with other uncontrolled malignancies;
2. Previously treated with any CAR-T cell product or other genetically-modified T cell therapy;
3. Patients with HIV infection, hepatitis B (HBsAg positive) or hepatitis C（anti-HCV positive);
4. Patients with central nervous system involvement by lymphoma ,malignant cells in cerebrospinal fluid or history of brain metastasis;
5. Patients with atrial or ventricular involvement by B-cell malignancies;
6. Patients with tumor mass require urgent treatment, such as ileus or vascular compression;
7. Patients with severe disease or other uncontrolled diseases that were not suitable for this trial, such as coronary heart disease, angina pectoris, myocardial infarction, arrhythmia, cerebral thrombosis, cerebral hemorrhage, grade 2-3 hypertension;
8. Unstable pulmonary embolism, deep venous embolism, or other major arterial/venous thromboembolism events occurred within 30 days prior to randomization. If patients receive anticoagulant therapy, the treatment dose must be stable prior to randomization;
9. Any situations that the investigators believes were not suitable for this trial;
10. Long-term use of immunosuppressive agents after organ transplantation, except for the patients recently or currently receiving inhaled steroids;
11. Pregnant(or lactation) women;
12. Patients with severe active infections(excluding simple urinary tract infection and bacterial pharyngitis)within 30 days prior to randomization

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Modified anti-CD19 CAR T cell therapy	Modified anti-CD19 CAR T cells	CAR T cell therapy

Primary Outcome Measures

Name	Time	Method
Dose-limiting toxicity (DLT)	Baseline up to 28 days after modified CD19 CAR-T cells infusion	Adverse events assessed according to NCI-CTCAE v5.0 criteria
Incidence of treatment-emergent adverse events [Safety and Tolerability]	Up to 5 years after modified CD19 CAR-T cells infusion	Adverse events assessed according to NCI-CTCAE v5.0 criteria

Secondary Outcome Measures

Name	Time	Method
B-cell malignancies, progression-free survival（PFS）	Up to 2 years after modified CD19 CAR-T cells infusion	From the first infusion of modified CD19 CAR-T cells to the occurrence of any event, including death, relapse, disease progression, and the last visit
B-cell malignancies, Overall survival	Up to 2 years after modified CD19 CAR-T cells infusion	From the first infusion of modified CD19 CAR-T cells to death or the last visit
B-cell malignancies, disease control rate (DCR)	Month 6,12,18 and 24	Assessment of DCR(DCR=CR+PR+SD)
B-cell malignancies, Overall response rate(ORR)	3 months, 6 months	Assessment of ORR(ORR=CR+PR)

Trial Locations

Locations (1)

Sichuan University; 🇨🇳 Chengdu, Sichuan, China