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

Refractory B-Cell Non-Hodgkin Lymphoma Clinical Trial

Official title:

Phase I, Open Label, Study of CXCR4 Modified CD19 CAR-T Therapy in Patients With Relapsed or Refractory CD19+ B-cell Malignancies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04684472
• Other study ID #: MCART-003
• Status: Recruiting
• Phase: Phase 1
• Start date: March 17, 2021
• Est. completion date: January 1, 2024

Study information

• Verified date: September 2022
• Source: Sichuan University
• Contact: pei shu, MD
• Phone: +86(028)85423525
• Email: peishu1991[@]sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 18
• Est. completion date: January 1, 2024
• Est. primary completion date: January 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma, B-Cell
• Refractory B-Cell Non-Hodgkin Lymphoma
• Refractory Leukemia

Intervention

Biological:
• Modified anti-CD19 CAR T cells
intravenous infusion

Locations

Country	Name	City	State
China	Sichuan University	Chengdu	Sichuan

Sponsors (1)

Lead Sponsor	Collaborator
Liqun Zou

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment-emergent adverse events [Safety and Tolerability]	Adverse events assessed according to NCI-CTCAE v5.0 criteria	Up to 5 years after modified CD19 CAR-T cells infusion
Primary	Dose-limiting toxicity (DLT)	Adverse events assessed according to NCI-CTCAE v5.0 criteria	Baseline up to 28 days after modified CD19 CAR-T cells infusion
Secondary	B-cell malignancies, Overall response rate(ORR)	Assessment of ORR(ORR=CR+PR)	3 months, 6 months
Secondary	B-cell malignancies, Overall survival	From the first infusion of modified CD19 CAR-T cells to death or the last visit	Up to 2 years after modified CD19 CAR-T cells infusion
Secondary	B-cell malignancies, progression-free survival(PFS)	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	Up to 2 years after modified CD19 CAR-T cells infusion
Secondary	B-cell malignancies, disease control rate (DCR)	Assessment of DCR(DCR=CR+PR+SD)	Month 6,12,18 and 24