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

Study Overview
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Brief Summary
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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).

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

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

Intervention / Treatment
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* Biological: Modified anti-CD19 CAR T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged 18-70 years; Estimated survival time ≥ 12 weeks; Histologically confirmed diagnosis of CD19+ B-ALL or CD19+ B-NHL(meeting one of the following conditions): Ineffectively or relapses after 2 or more remedial treatments Relapse after auto-HSCT or unsuitable for auto-HSCT; At least one assessable tumor lesion; ECOG performance status 0 to 2; 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; Male and female of reproductive potential must agree to use birth control during the study and for at least 30 days post study; Patients or their legal guardians volunteer to participate in the study and sign the informed consent. Exclusion Criteria: Patients with other uncontrolled malignancies; Previously treated with any CAR-T cell product or other genetically-modified T cell therapy; Patients with HIV infection, hepatitis B (HBsAg positive) or hepatitis C（anti-HCV positive); Patients with central nervous system involvement by lymphoma ,malignant cells in cerebrospinal fluid or history of brain metastasis; Patients with atrial or ventricular involvement by B-cell malignancies; Patients with tumor mass require urgent treatment, such as ileus or vascular compression; 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; 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; Any situations that the investigators believes were not suitable for this trial; Long-term use of immunosuppressive agents after organ transplantation, except for the patients recently or currently receiving inhaled steroids; Pregnant(or lactation) women; Patients with severe active infections(excluding simple urinary tract infection and bacterial pharyngitis)within 30 days prior to randomization

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Modified anti-CD19 CAR T cell therapy<br>CAR T cell therapy | Biological: Modified anti-CD19 CAR T cells<br>* intravenous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| B-cell malignancies, Overall response rate(ORR) | Assessment of ORR(ORR=CR+PR) | 3 months, 6 months | 
| 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 | 
| 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 | 
| B-cell malignancies, disease control rate (DCR) | Assessment of DCR(DCR=CR+PR+SD) | Month 6,12,18 and 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Modified CD19 CAR-T