Non-Hodgkin's B-cell Lymphoma
Conditions
Brief summary
The trial is a single arm, single-center, non-randomized phase I clinical trial which is designed to evaluate the safety and efficacy of C-CAR039 in treatment of relapsed or refractory NHL patients
Detailed description
This study plans to enroll 25 patients to assess the safety and efficacy of C-CAR039. Subjects who meet the eligibility criteria will receive a single dose of C-CAR039 injection. The study will include the following sequential phases: Screening, Apheresis and C-CAR039 manufacturing, Bridging (if needed), Baseline, lymphodepletion, C-CAR039 infusion, and Follow-up Visit.
Interventions
BIOLOGICALPrizloncabtagene Autoleucel
Autologous 2nd generation CD19/CD20-directed CAR-T cells, single infusion intravenously
Sponsors
Shanghai AbelZeta Ltd.
Shanghai Tongji Hospital, Tongji University School of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 1\. Volunteered to participate in this study and signed informed consent * 2\. Age 18-75 years old, male or female * 3\. CD19 or CD20 positive DLBCL (including PMBCL and tFL), FL and MCL confirmed by cytology or histology according to WHO2016 criteria. For CD20-positive subjects, they should have received at least one regimen containing anti-CD20-targeted therapy (such as rituximab). If they do not complete the regimen due to intolerance, the cause should be recorded. * 4\. Relapsed or refractory disease after ≥ 2 lines (for FL, at least 3 lines) of standard therapy or relapsed after autologous stem cell transplantation (ASCT) * 5\. At least one measurable lesion (LDi ≥ 1.5 cm); * 6\. At least two weeks from last treatment (radiation, chemotherapy, mAb, etc) to apheresis; * 7\. LVEF≥ 50% (ECHO) * 8\. No active pulmonary infections, normal or mild impaired pulmonary function and SpO2≥92% * 9\. Laboratory criteria: ANC≥1.0×109/L; Platelets≥50×109/L; Serum total bilirubin ≤1.5x ULN; Creatinine≤ ULN; AST and ALT≤3x ULN * 10\. No contraindications of apheresis; * 11\. Expected survival ≥ 3months * 12\. ECOG score 0 or 1
Exclusion criteria
* 1\. Have a history of allergy to cellular products; * 2\. According to the NYHA cardiac function grading standards, patients with grade III or IV cardiac dysfunction; * 3\. A history of craniocerebral trauma, disturbance of consciousness, epilepsy, cerebrovascular ischemia, cerebrovascular hemorrhagic disease, etc.; * 4\. Patients with central nervous system involvement; * 5\. Patients with autoimmune diseases, immunodeficiency or other conditions requiring immunosuppressive therapy; * 6\. Received allogeneic hematopoietic stem cell transplantation before; * 7\. Previous use of any CAR T cell product or other genetically modified T cell therapy; * 8\. Autologous stem cell transplantation within 6 weeks before infusion; * 9\. Severe active infections (except for simple urinary tract infections, bacterial pharyngitis), or currently undergoing intravenous infusion of antibiotics. However, prophylactic antibiotic, antiviral and antifungal infection treatments are permissible; * 10\. Live vaccination within 4 weeks prior to apheresis; * 11\. People infected with HIV, HBV, HCV and TPPA/RPR, and carriers with HBV; * 12\. A history of alcohol abuse, drug use or mental illness; * 13\. Subjects who are not sterilized and have any of the following conditions: 1. are pregnant/lactating; or 2. planned pregnancy during the trial; or 3. being fertile and unable to use effective contraception; * 14\. Severe hypersensitivity to fludarabine or cyclophosphamide; * 15\. A history of other primary cancers other than the following: 1. Non-melanoma tumors such as basal cell carcinoma of the skin that are cured by excision 2. Cured in situ cancers such as cervical, bladder, or breast cancer * 16\. The investigators consider that the subject has other conditions that are not suitable for this trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of adverse events | Up to 12 weeks after C-CAR039 infusion | Incidence and severity of adverse events after CAR-T infusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response rate (ORR) | Up to 24 Months after C-CAR039 infusion | Complete response (CR) rate plus partial response (PR) rate by Lugano 2014 criteria |
| Duration of response (DOR) | Up to 24 Months after C-CAR039 infusion | The time from the date of first response (PR or CR) to the date of disease progression or death after C-CAR039 infusion |
| Progression-free survival (PFS) | Up to 24 Months after C-CAR039 infusion | The time from C-CAR039 infusion to the date of progression as assessed by Lugano 2014 criteria or death |
| Overall survival (OS) | Up to 24 Months after C-CAR039 infusion | The time from C-CAR039 infusion to the date of death |
Countries
China
Outcome results
None listed