Non-Hodgkin's B-cell Lymphoma
Conditions
Brief summary
This is a single-arm, open label, dose escalation, phase I study of C-CAR039 in adults with relapsed/refractory B-cell Non-Hodgkin's Lymphoma.
Detailed description
This is a single-arm, open label, 3+3 dose escalation, phase I study to evaluate the safety and preliminary efficacy of C-CAR039 in adults with relapsed/refractory B-cell Non-Hodgkin's Lymphoma. 10 patients are planned to be enrolled. Following consent, enrolled subjects will undergo a leukapheresis procedure to collect autologous mononuclear cells for manufacture of C-CAR039. Following manufacture of the drug product, subjects will receive lymphodepleting therapy with fludarabine and cyclophosphamide prior to C-CAR039 infusion. All subjects who have received C-CAR039 infusion will be followed for up to 24 months.
Interventions
BIOLOGICALPrizloncabtagene Autoleucel
Autologous 2nd generation CD19/CD20-directed CAR-T cells, single infusion intravenously
Sponsors
Shanghai AbelZeta Ltd.
First Affiliated Hospital of Zhejiang University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
None (Open Label)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. The patient volunteered to participate in the study and signed the Informed Consent; 2. Age between 18 and 70 (including 18 and 70), male or female; 3. Expected survival ≥ 12 weeks; 4. ECOG score 0-2 5. CD19 or CD20 positive B-NHL confirmed by cytology or histology according to WHO2016 criteria, including DLBCL, PMBCL, tFL, FL and MCL; 6. Relapsed or refractory disease after ≥ 2 lines (for FL, at least 3 lines) of standard therapy or relapsed after autologous stem cell transplantation (ASCT) 7. 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 of intolerance should be recorded; 8. No contraindications of apheresis; 9. At least one measurable lesion according to Lugano 2014 criteria; 10. Adequate organ function.
Exclusion criteria
1. Malignant tumors other than B-NHL within 5 years prior to screening, except cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after radical surgery, and breast ductal carcinoma in situ after radical surgery; 2. Active HIV, HBV, HCV or treponema pallidum infection ; 3. Any instability of systemic disease, including but not limited to active infection (except local infection), severe cardiac, liver, kidney, or metabolic disease need therapy; 4. Any uncontrolled, active disease that prevents participation in the trial; 5. Female subjects who have been pregnant or breastfeeding, or who plan to conceive during or within 1 year after treatment, or male subjects' partner plans to conceive within 1 year after their cell transfusion; 6. Active or uncontrolled infections requiring systemic treatment within 14 days before enrollment; 7. Patients who have been previously infected with tuberculosis; 8. Administered Corticosteroids and/or other immunosuppressants within 7 days before apheresis. and 5 days before the infusion of C-CAR039; 9. Patients with central nervous system involvement; 10. Any systemic antitumor therapy was performed within 2 weeks before conditional treatment chemotherapy pretreatment; 11. Any situation that the investigator believes would compromise the safety of the subject or interfere with the purpose of the study; 12. Those with medical conditions that prevent them from signing the written informed consent or from complying with the study procedures; or those who are unwilling or unable to comply with the study requirements. 13. Other conditions deemed unsuitable for enrollment by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MTD | Up to 24 months after C-CAR039 infusion | maximum tolerated dose or clinical recommended dose |
| DLT | Up to 28 days after C-CAR039 infusion | Dose limiting toxicity |
| AE/SAE/AESI | Up to 24 months after C-CAR039 infusion | adverse events (AE), serious adverse event (SAE), adverse events of sepical interest (AESI) (including cytokine release syndrome (CRS), and nerve toxicity), laboratory tests (type, frequency and severity), vital signs and ECG abnormality rate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| C-CAR039 CAR expansion and persistence | Up to 24 Months after C-CAR039 infusion | After C-CAR039 infusion, peripheral blood EXP039 CAR expansion and persistence in vivo, including Cmax, Tmax, AUC0-28day, Tlast |
| Overall survival (OS) | Up to 24 Months after C-CAR039 infusion | The time from C-CAR039 infusion to the date of death |
| 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 better) to the date of disease progression or death after C-CAR039 infusion |
Countries
China
Outcome results
None listed