Clinical trial NCT04684472: Modified CD19 CAR-T in Patients With Relapsed or Refractory CD19+ B-cell Malignancies
Official title: Phase I, Open Label, Study of CXCR4 Modified CD19 CAR-T Therapy in Patients With Relapsed or Refractory CD19+ B-cell Malignancies
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Refractory B-Cell Non-Hodgkin Lymphoma
Refractory Leukemia
Keywords: Modified CD19 CAR-T
Lead sponsor: Sichuan University
Sponsor class: OTHER
First posted: 2020-12-24
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of treatment-emergent adverse events [Safety and Tolerability]
timeFrame: Up to 5 years after modified CD19 CAR-T cells infusion
measure: Dose-limiting toxicity (DLT)
timeFrame: Baseline up to 28 days after modified CD19 CAR-T cells infusion
Secondary outcomes:
measure: B-cell malignancies, Overall response rate(ORR)
timeFrame: 3 months, 6 months
measure: B-cell malignancies, Overall survival
timeFrame: Up to 2 years after modified CD19 CAR-T cells infusion
measure: B-cell malignancies, progression-free survival（PFS）
timeFrame: Up to 2 years after modified CD19 CAR-T cells infusion
measure: B-cell malignancies, disease control rate (DCR)
timeFrame: Month 6,12,18 and 24
Other outcomes:
Locations:
city: Chengdu
country: China
facility: Sichuan University
state: Sichuan
Study officials:
affiliation: Sichuan University
name: liqun zou, phd
role: PRINCIPAL_INVESTIGATOR
References: