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

Phase 1

Active, not recruiting

• Conditions: Non-Hodgkin's B-cell Lymphoma
• Interventions: Biological: Prizloncabtagene Autoleucel

• Registration Number: NCT04693676
• Lead Sponsor: First Affiliated Hospital of Zhejiang University

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.

Study Timeline

• Study Start: 2020-08-03
• Study First Submitted: 2020-12-03
• Study First Submitted QC: 2020-12-31
• Study First Posted: 2021-01-05
• Status Verified: 2023-05
• Last Update Submitted: 2023-09-25
• Last Update Posted: 2023-09-28
• Primary Completion: 2023-12-31
• Study Completion: 2024-04-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 17

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Prizloncabtagene autoleucel	Prizloncabtagene Autoleucel	Prizlon-cel will be intravenously administered as a single infusion after lymphodepletion

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
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

Trial Locations

Locations (1)

The First Affiliated Hospital, College of Medicine, Zhejiang University; 🇨🇳 Hangzhou, Zhejiang, China