A Study of C-CAR039 (Prizloncabtagene Autoleucel) in Patients with Relapsed/Refractory Large B-Cell Lymphoma

Phase 1

Recruiting

• Conditions: Relapsed/Refractory Large B-Cell Lymphoma
• Interventions: Biological: Prizloncabtagene autoleucel

• Registration Number: NCT05800977
• Lead Sponsor: Shanghai AbelZeta Ltd.

Brief Summary

This is a multicenter, single arm, open-label study. The purpose of the study is to evaluate safety of Prizloncabtagene Autoleucel (Prizlon-cel) and establish the recommended Phase 2 dose (RP2D) (Phase 1b) and to evaluate the efficacy of Prizlon-cel (Phase 2) in patients with relapsed or refractory large b-cell lymphoma (LBCL).

Detailed Description

The purpose of the study is to evaluate the safety and efficacy of Prizlon-cel. It includes two phases, Phase 1b and Phase 2. In Phase 1b study, RP2D will be determined. The selected dose will be further evaluated in the Phase 2 study. The study includes the following sequential procedures: Screening, Apheresis and CAR-T manufacturing, Baseline, Lymphodepletion, CAR-T infusion, DLT period (Phase 1b) and Follow-up Visit. Subjects will be followed for at least 2 years after Prizlon-cel infusion, with up to 15 years long-term follow-up on a separate study.

Study Timeline

• Study Start: 2023-02-22
• Study First Submitted: 2023-03-24
• Study First Submitted QC: 2023-03-24
• Study First Posted: 2023-04-06
• Status Verified: 2024-09
• Last Update Submitted: 2024-11-04
• Last Update Posted: 2024-11-06
• Primary Completion: 2025-10-31
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 112

Inclusion Criteria

• ≥ 18 years of age

• Histologically confirmed CD19 or CD20 positive B-cell non-Hodgkin lymphoma, including the following neoplasms as defined by the 2016 WHO classification of lymphoid neoplasms:

  1. Diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS)
  2. Primary mediastinal large B-cell lymphoma (PMBCL)
  3. Transformed follicular lymphoma (tFL)
  4. High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements (HGBL-DH/TH)
  5. High-grade B-cell lymphoma, NOS (HGBL, NOS)
  6. Follicular lymphoma grade 3B (FL3B)

• Relapsed or refractory disease after ≥ 2 lines of standard therapy or relapsed after autologous stem cell transplantation (ASCT)

• At least one measurable lesion per the Lugano 2014 Classification

• Adequate organ and marrow function

Exclusion Criteria

• Prior allogeneic hematopoietic stem cell transplantation (HSCT) at anytime, or ASCT within 12 weeks prior to apheresis
• Suspected or confirmed central nervous system involvement
• Stroke or convulsion history within 6 months of signing informed consent form (ICF)
• Autoimmune disease, immunodeficiency or diseases requiring immunosuppressants treatment
• Uncontrolled active infection
• Positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with detectable hepatitis B virus (HBV) DNA in peripheral blood; positive hepatitis C virus (HCV) antibody with positive HCV RNA in peripheral blood; positive human immunodeficiency virus (HIV) antibody; positive syphilis test
• Severe heart, liver, renal or metabolism disease
• Inadequate wash-out time for previous anti-tumor treatments prior to apheresis
• Prior CAR-T therapy

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
Phase 1b: Recommended Phase 2 Dose (R2PD)	Up to 2 years after C-CAR039 infusion	Based on DLTs rates and overall safety profile
Phase 1b: Incidence and Severity of Adverse Events (AEs)	Up to 2 years after C-CAR039 infusion	Incidence and severity of any AEs , including dose limiting toxicities (DLTs)
Phase 2: Overall Response Rate (ORR) at 3 months	Up to 3 months after C-CAR039 infusion	Best response rate at 3 months after C-CAR039 infusion, including partial response (PR) and complete response (CR)

Secondary Outcome Measures

Name	Time	Method
ORR at 6 months	Up to 6 months after C-CAR039 infusion	Best response rate at 6 months after C-CAR039 infusion, including PR and CR
The B cell percentage changes and CD19/CD20 expression changes in blood	Up to 2 years after C-CAR039 infusion	The B cell percentage changes and CD19/CD20 expression changes in blood by flow cytometry assay before and after C-CAR039 infusion
Time to response (TTR)	Up to 2 years after C-CAR039 infusion	The time from the date of C-CAR039 infusion to the first documented PR or CR
Area under the curve within 28 days (AUC0-28d)	Up to 28 days after C-CAR039 infusion	Area under the curve of C-CAR039 in peripheral blood within 28 days post infusion
Phase 2: Incidence and Severity of Adverse Events (AEs)	Up to 2 years after C-CAR039 infusion	Incidence and severity of any AEs
Progression-free survival (PFS)	Up to 2 years after C-CAR039 infusion	The time from the date of C-CAR039 infusion to the date of first documented disease progression or death
Overall survival (OS)	Up to 2 years after C-CAR039 infusion	The time from the date of C-CAR039 infusion to the date of death
Maximal plasma concentration (Cmax)	Up to 2 years after C-CAR039 infusion	Maximal plasma concentration of C-CAR039 in peripheral blood
Phase 1b: ORR at 3 months	Up to 3 months after C-CAR039 infusion	Best response rate at 3 months after C-CAR039 infusion, including PR and CR
ORR	Up to 2 years after C-CAR039 infusion	Best response, including PR and CR
Time of last measurable observed concentration (Tlast)	Up to 2 years after C-CAR039 infusion	Time of last measurable observed concentration of C-CAR039 in peripheral blood
Duration of response (DOR)	Up to 2 years after C-CAR039 infusion	The time from the first documented PR or CR to disease progression or death, whichever occurs first
Time to reach the maximal plasma concentration (Tmax)	Up to 2 years after C-CAR039 infusion	Time to reach the maximal plasma concentration of C-CAR039 in peripheral blood
Anti-drug (C-CAR039) antibody	Up to 2 years after C-CAR039 infusion	Presence of serum anti-drug (C-CAR039) antibody

Trial Locations

Locations (15)

Beijing Cancer Hospital; 🇨🇳 Beijing, China

Beijing GoBroad Hospital; 🇨🇳 Beijing, China

Peking University Third Hospital; 🇨🇳 Beijing, China

Chongqing University Cancer Hospital; 🇨🇳 Chongqing, China

Guangdong Provincial People's Hospital; 🇨🇳 Guangzhou, China

Zhujiang Hospital of Southern Medical University; 🇨🇳 Guangzhou, China

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

Cancer Hospital of Shandong First Medical University; 🇨🇳 Jinan, China

Jiangxi Cancer Hospital; 🇨🇳 Nanchang, China

Jiangsu Province Hospital; 🇨🇳 Nanjing, China

Ruijin Hospital, Shanghai Jiaotong University School of Medicine; 🇨🇳 Shanghai, China

Chinese Academy of Medical Sciences Hematology Hospital; 🇨🇳 Tianjin, China

Tianjin Medical University Cancer Institute& Hospital; 🇨🇳 Tianjin, China

Henan Cancer Hospital; 🇨🇳 Zhengzhou, China

The First Affiliated Hospital of Zhengzhou University; 🇨🇳 Zhengzhou, China