A Study Evaluating Safety and Efficacy of C-CAR039 Treatment in NHL Subjects

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

The trial is a single arm, single-center, non-randomized phase I clinical trial which is designed to evaluate the safety and efficacy of C-CAR039 in treatment of relapsed or refractory NHL patients

Study Overview

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

Detailed Description

This study plans to enroll 25 patients to assess the safety and efficacy of C-CAR039. Subjects who meet the eligibility criteria will receive a single dose of C-CAR039 injection.

The study will include the following sequential phases: Screening, Apheresis and C-CAR039 manufacturing, Bridging (if needed), Baseline, lymphodepletion, C-CAR039 infusion, and Follow-up Visit.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200065
      • Shanghai Tongji Hospital, Tongji University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Volunteered to participate in this study and signed informed consent
• 2. Age 18-75 years old, male or female
• 3. CD19 or CD20 positive DLBCL (including PMBCL and tFL), FL and MCL confirmed by cytology or histology according to WHO2016 criteria. 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 should be recorded.
• 4. Relapsed or refractory disease after ≥ 2 lines (for FL, at least 3 lines) of standard therapy or relapsed after autologous stem cell transplantation (ASCT)
• 5. At least one measurable lesion (LDi ≥ 1.5 cm);
• 6. At least two weeks from last treatment (radiation, chemotherapy, mAb, etc) to apheresis;
• 7. LVEF≥ 50% (ECHO)
• 8. No active pulmonary infections, normal or mild impaired pulmonary function and SpO2≥92%
• 9. Laboratory criteria: ANC≥1.0×109/L; Platelets≥50×109/L; Serum total bilirubin ≤1.5x ULN; Creatinine≤ ULN; AST and ALT≤3x ULN
• 10. No contraindications of apheresis;
• 11. Expected survival ≥ 3months
• 12. ECOG score 0 or 1

Exclusion Criteria:

• 1. Have a history of allergy to cellular products;
• 2. According to the NYHA cardiac function grading standards, patients with grade III or IV cardiac dysfunction;
• 3. A history of craniocerebral trauma, disturbance of consciousness, epilepsy, cerebrovascular ischemia, cerebrovascular hemorrhagic disease, etc.;
• 4. Patients with central nervous system involvement;
• 5. Patients with autoimmune diseases, immunodeficiency or other conditions requiring immunosuppressive therapy;
• 6. Received allogeneic hematopoietic stem cell transplantation before;
• 7. Previous use of any CAR T cell product or other genetically modified T cell therapy;
• 8. Autologous stem cell transplantation within 6 weeks before infusion;
• 9. Severe active infections (except for simple urinary tract infections, bacterial pharyngitis), or currently undergoing intravenous infusion of antibiotics. However, prophylactic antibiotic, antiviral and antifungal infection treatments are permissible;
• 10. Live vaccination within 4 weeks prior to apheresis;
• 11. People infected with HIV, HBV, HCV and TPPA/RPR, and carriers with HBV;
• 12. A history of alcohol abuse, drug use or mental illness;

• 13. Subjects who are not sterilized and have any of the following conditions:

  1. are pregnant/lactating; or
  2. planned pregnancy during the trial; or
  3. being fertile and unable to use effective contraception;
• 14. Severe hypersensitivity to fludarabine or cyclophosphamide;

• 15. A history of other primary cancers other than the following:

  1. Non-melanoma tumors such as basal cell carcinoma of the skin that are cured by excision
  2. Cured in situ cancers such as cervical, bladder, or breast cancer
• 16. The investigators consider that the subject has other conditions that are not suitable for this trial.

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	Incidence and severity of adverse events after CAR-T infusion	Up to 12 weeks after C-CAR039 infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Duration of response (DOR)	The time from the date of first response (PR or CR) to the date of disease progression or death after C-CAR039 infusion	Up to 24 Months after C-CAR039 infusion

Collaborators and Investigators

• Sponsor: Shanghai Tongji Hospital, Tongji University School of Medicine
• Collaborators: Cellular Biomedicine Group Ltd.
• Investigators: Principal Investigator: Aibin Liang, MD, Ph.D, Shanghai Tongji Hospital, Tongji University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2019
• Primary Completion (Estimated): June 30, 2023
• Study Completion (Estimated): December 30, 2023

Study Registration Dates

• First Submitted: March 20, 2020
• First Submitted That Met QC Criteria: March 20, 2020
• First Posted (Actual): March 23, 2020

Study Record Updates

• Last Update Posted (Actual): May 26, 2023
• Last Update Submitted That Met QC Criteria: May 24, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• 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: 0702-015

Drug and device information, study documents

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