A Study of C-CAR039 in Subjects With Relapsed and/or Refractory B Cell Non-Hodgkin's Lymphoma

A Phase 1 Study of CD19 and CD20 Targeted Chimeric Antigen Receptor T Cells Therapy (C-CAR039) in Subjects With Relapsed and/or Refractory B Cell Non-Hodgkin's Lymphoma

This is a single-center, open-label study to evaluate the safety and efficacy of C-CAR039 in relapsed and/or refractory B cell Non-Hodgkin's Lymphoma patients.

Study Overview

• Status: Completed
• Conditions: B Cell Non-Hodgkin's Lymphoma
• Intervention / Treatment: Biological: CD19/CD20-directed Chimeric Antigen Receptor T Cells

Detailed Description

The study includes the following sequential phases: Screening, Apheresis and C-CAR039 manufacturing, Baseline testing, Lymphodepletion, C-CAR039 infusion, Dose-limiting toxicity observation and Follow-up Visit.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Peking University Cancer Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. The patient volunteered to participate in the study and signed the Informed Consent;
2. Age, 18-70 years (include 18 and 70), male or female;
3. Expected survival ≥ 12 weeks
4. Eastern Cooperative Oncology Group score 0-2
5. CD19 or CD20 positive B-Non-Hodgkin's lymphoma confirmed by cytology or histology according to World Health Organization 2016 criteria;

6. Patients with a clear diagnosis of relapsed and/or refractory B-Non-Hodgkin's lymphoma, including Diffuse Large B Cell Lymphoma, Follicular Lymphoma and Mantle Cell Lymphoma. Diffuse Large B Cell Lymphoma includes the following types:

   1. Diffuse Large B Cell Lymphoma, Non Specifically
   2. Primary Mediastinal B-cell Lymphoma
   3. Transformed Follicular Lymphoma
   4. High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6
   5. High Grade B-Cell Lymphoma, Non Specifically
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 and adequate bone marrow reserve

    1. Hemoglobin≥80 g/L
    2. Absolute neutrophil count≥1.0×109/L
    3. Platelet≥50×109/L,
    4. Creatinine≤1.5×upper limit of the normal range (ULN)
    5. Cardiac ejection fraction≥50%
    6. Saturation of Pulse Oxygen>92%
    7. Total bilirubin≤1.5×ULN
    8. Alanine Aminotransferase/Aspartate Aminotransferase≤3×ULN

Exclusion Criteria:

1. Malignant tumors other than B-Non-Hodgkin's lymphoma 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. Human Immunodeficiency Virus, Hepatitis B Virus, Hepatitis C Virus 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 treatment;
4. 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;
5. Active or uncontrolled infections requiring systemic treatment within 14 days before enrollment;
6. Patients who have been previously infected with tuberculosis;
7. Administered Corticosteroids and/or other immunosuppressants within 7 days before apheresis. and 5 days before the infusion of C-CAR039;
8. Patients with central nervous system involvement;

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: C-CAR039; Autologous C-CAR039 administered by intravenous (IV) infusion	Biological: CD19/CD20-directed Chimeric Antigen Receptor T Cells; Autologous 2nd generation CD19/CD20-directed Chimeric Antigen Receptor T Cells, single infusion intravenously; Other Names: C-CAR039

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Observation	Incidence of adverse events after C-CAR039 infusion. Incidence and severity of adverse events according to NCI-CTCAE v5.0 criteria, including Dose Limited Toxicity	up to 24 Months. Incidence and severity of adverse events after C-CAR039 infusion according to National Cancer Institute Common Terminology Criteria for Adverse Events v5.0 criteria, including dose-limiting toxicity (DLT) and laboratory abnormalities.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum concentration (Cmax) of C-CAR039 in the peripheral blood.	Detect Chimeric Antigen Receptor-T copies number by quantitative polymerase chain reaction(qPCR).	Baseline, Days 4, 7, 10 and weeks 2, 3, 4, 8, 12 and month 6, 9, 12, 15, 18, 21, 24
Time to maximum concentration (Tmax) of C-CAR039 in the peripheral blood.	Detect Chimeric Antigen Receptor-T copies number by qPCR.	Baseline, Days 4, 7, 10 and weeks 2, 3, 4, 8, 12 and month 6, 9, 12, 15, 18, 21, 24
Peripheral blood duration of C-CAR039 in the peripheral blood after infusion.	Detect Chimeric Antigen Receptor-T copies number by qPCR.	Baseline, Days 4, 7, 10 and weeks 2, 3, 4, 8, 12 and month 6, 9, 12, 15, 18, 21, 24
Area under the curve 0h-28d of C-CAR039 in the peripheral blood.	Detect Chimeric Antigen Receptor-T copies number by qPCR.	Baseline, Days 4, 7, 10 and weeks 2, 3, 4
Overall response rate (ORR)	Complete response (CR) rate plus partial response (PR) rate by Lugano 2014 criteria.	4 weeks, 12 weeks, 6 months, 9 months, 12 months, 15 months, 18 months, 21 months, 24 months
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
Progression-free survival (PFS)	The time from C-CAR039 infusion to the date of progression as assessed by Lugano 2014 criteria or death.	4 weeks, 12 weeks, 6 months, 9 months, 12 months, 15 months, 18 months, 21 months, 24 months
Overall survival (OS)	The time from C-CAR039 infusion to the date of death.	up to 24 months

Collaborators and Investigators

• Sponsor: Peking University
• Collaborators: Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2021
• Primary Completion (Actual): January 30, 2024
• Study Completion (Actual): May 30, 2024

Study Registration Dates

• First Submitted: November 9, 2021
• First Submitted That Met QC Criteria: November 24, 2021
• First Posted (Actual): December 8, 2021

Study Record Updates

• Last Update Posted (Actual): January 30, 2026
• Last Update Submitted That Met QC Criteria: January 28, 2026
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: CD19/CD20-directed Chimeric Antigen Receptor T Cells
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Hemic and Lymphatic Diseases; Lymphoma, B-Cell
• Other Study ID Numbers: 0702-022

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
• product manufactured in and exported from the U.S.: No