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

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

This is a single-center, open-label study to evaluate the safety and efficacy of C-CAR039 in relapsed and/or refractory B-NHL patients.

Study Overview

• Status: Active, not recruiting
• Conditions: Non-Hodgkin's B-cell Lymphoma
• Intervention / Treatment: Biological: Prizloncabtagene autoleucel

Detailed Description

This is a single-arm, open label, 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 Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Lanfang Li, PhD&MD; Phone Number: 022-23340123-3210; Email: lilanfangmeng@163.com
• Study Contact Backup: Name: Jing Zhao; Phone Number: 022-23340123-3210; Email: sharry4601@126.com

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Tianjin Medical University Cancer Institute & Hosipital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18-70 years (include 18 and 70), male or female;
2. Expected survival ≥ 12 weeks
3. ECOG score 0-2
4. CD19 or CD20 positive B-NHL confirmed by cytology or histology according to WHO2016 criteria, including DLBCL, PMBCL, tFL, FL and MCL;
5. Relapsed or refractory disease after ≥ 2 lines (for FL, at least 3 lines) of standard therapy or relapsed after autologous stem cell transplantation (ASCT)
6. 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;
7. No contraindications of apheresis.
8. At least one measurable lesion according to Lugano 2014 criteria;
9. Adequate organ and bone marrow function.
10. The patient volunteered to participate in the study and signed the Informed Consent;

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. Any situation that the investigator believes will harm the safety of the subjects or interfere with the purpose of the study
6. 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 C-CAR039 infusion;
7. Active or uncontrolled infections requiring systemic treatment within 14 days before enrollment;
8. Patients who have been previously infected with tuberculosis;
9. Administered Corticosteroids and/or other immunosuppressants within 7 days before apheresis. and 5 days before the infusion of C-CAR039;
10. Patients with central nervous system involvement;
11. Any systemic antitumor therapy performed within 2 weeks before enrollment;
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 was considered unsuitable for enrollment by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prizloncabtagene autoleucel; Prizlon-cel will be intravenously administered as a single infusion after lymphodepletion.	Biological: Prizloncabtagene autoleucel; Autologous 2nd generation CD19/CD20-directed CAR-T cells, single infusion intravenously; Other Names: C-CAR039

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of adverse events (AE)	Incidence and severity of adverse events, including AE, Serious AE, AE of special interset (AESI)	Up to 24 months after C-CAR039 infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Maximum concentration of C-CAR039 in the peripheral blood (Cmax)	Detect CAR-T copies number by qPCR	Up to 24 Months after C-CAR039 infusion
The last of C-CAR039 in the peripheral blood after infusion (Tlast)	Detect CAR-T copies number by qPCR	Up to 24 Months after C-CAR039 infusion
AUC0-28d of C-CAR039 in the peripheral blood (AUC0-28d)	Detect CAR-T copies number by qPCR	Up to 28 days after C-CAR039 infusion
Time to reach the maximum plasma concentration (Tmax)	Detect CAR-T copies number by qPCR	Up to 24 Months after C-CAR039 infusion

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital
• Collaborators: Cellular Biomedicine Group Ltd.
• Investigators: Principal Investigator: Lanfang Li, PhD&MD, Tianjin Medical University Cancer Institute & Hosipital

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2020
• Primary Completion (Estimated): July 31, 2023
• Study Completion (Estimated): December 30, 2023

Study Registration Dates

• First Submitted: November 30, 2020
• First Submitted That Met QC Criteria: January 5, 2021
• First Posted (Actual): January 6, 2021

Study Record Updates

• Last Update Posted (Actual): May 31, 2023
• Last Update Submitted That Met QC Criteria: May 28, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: CD19/CD20-directed CAR-T cells
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell
• Other Study ID Numbers: 0702-021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No