A Study of C-CAR039 Treatment in Subjects With r/r NHL Subjects Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 1 Study Evaluating Safety and Efficacy of C-CAR039 Treatment in Subjects With Relapsed and/or Refractory NHL

Conditions
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Non-Hodgkin's B-cell Lymphoma

Intervention / Treatment
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* Biological: Prizloncabtagene Autoleucel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient volunteered to participate in the study and signed the Informed Consent; Age between 18 and 70 (including 18 and 70), male or female; Expected survival ≥ 12 weeks; ECOG score 0-2 CD19 or CD20 positive B-NHL confirmed by cytology or histology according to WHO2016 criteria, including DLBCL, PMBCL, tFL, FL and MCL; Relapsed or refractory disease after ≥ 2 lines (for FL, at least 3 lines) of standard therapy or relapsed after autologous stem cell transplantation (ASCT) 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; No contraindications of apheresis; At least one measurable lesion according to Lugano 2014 criteria; Adequate organ function. Exclusion Criteria: 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; Active HIV, HBV, HCV or treponema pallidum infection ; Any instability of systemic disease, including but not limited to active infection (except local infection), severe cardiac, liver, kidney, or metabolic disease need therapy; Any uncontrolled, active disease that prevents participation in the trial; 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; Active or uncontrolled infections requiring systemic treatment within 14 days before enrollment; Patients who have been previously infected with tuberculosis; Administered Corticosteroids and/or other immunosuppressants within 7 days before apheresis. and 5 days before the infusion of C-CAR039; Patients with central nervous system involvement; Any systemic antitumor therapy was performed within 2 weeks before conditional treatment chemotherapy pretreatment; Any situation that the investigator believes would compromise the safety of the subject or interfere with the purpose of the study; 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. Other conditions deemed unsuitable for enrollment by the investigator.

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: Prizloncabtagene autoleucel<br>Prizlon-cel will be intravenously administered as a single infusion after lymphodepletion | Biological: Prizloncabtagene Autoleucel<br>* Autologous 2nd generation CD19/CD20-directed CAR-T cells, single infusion intravenously<br>* Other names: C-CAR039;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MTD | maximum tolerated dose or clinical recommended dose | Up to 24 months after C-CAR039 infusion | 
| DLT | Dose limiting toxicity | Up to 28 days after C-CAR039 infusion | 
| AE/SAE/AESI | 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. | Up to 24 months after C-CAR039 infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| C-CAR039 CAR expansion and persistence | After C-CAR039 infusion, peripheral blood EXP039 CAR expansion and persistence in vivo, including Cmax, Tmax, AUC0-28day, Tlast | Up to 24 Months after C-CAR039 infusion | 
| Overall response rate (ORR) | Complete response (CR) rate plus partial response (PR) rate by Lugano 2014 criteria | Up to 24 Months after C-CAR039 infusion | 
| Duration of response (DOR) | The time from the date of first response (PR or better) to the date of disease progression or death after C-CAR039 infusion | Up to 24 Months after C-CAR039 infusion | 
| Progression-free survival (PFS) | The time from C-CAR039 infusion to the date of progression as assessed by Lugano 2014 criteria or death | Up to 24 Months after C-CAR039 infusion | 
| Overall survival (OS) | The time from C-CAR039 infusion to the date of death | Up to 24 Months after C-CAR039 infusion |