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

A Phase 1b/2 Study of a Anti-CD19/CD20 Bispecific CAR-T Therapy (C-CAR039/Prizloncabtagene Autoleucel) in Patients With Relapsed/Refractory Large B-Cell Lymphoma

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).

Study Overview

• Status: Recruiting
• Conditions: Relapsed/Refractory Large B-Cell Lymphoma
• Intervention / Treatment: Biological: Prizloncabtagene autoleucel

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 Type: Interventional
• Enrollment (Anticipated): 72
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Yuqin Song, M.D., PhD; Phone Number: 86-10-88196116; Email: SongYQ_VIP@163.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Peking Cancer Hospital
    • Contact: Yuqin Song, M.D., PhD
  • Hangzhou, China
    • Recruiting
    • The first Affiliated Hospital, Zhejiang University School of Medicine
    • Contact: Jie Jin, M.D., PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 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; Prizlon-cel is a novel 2nd generation 4-1BB bispecific chimeric antigen receptor T-cell (CAR-T) targeting both CD19 and CD20 antigens; Other Names: C-CAR039

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Cellular Biomedicine Group Ltd.
• Investigators: Principal Investigator: Yuqin Song, M.D., PhD, Peking Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2023
• Primary Completion (Anticipated): March 31, 2027
• Study Completion (Anticipated): March 31, 2027

Study Registration Dates

• First Submitted: March 24, 2023
• First Submitted That Met QC Criteria: March 24, 2023
• First Posted (Actual): April 6, 2023

Study Record Updates

• Last Update Posted (Actual): April 6, 2023
• Last Update Submitted That Met QC Criteria: March 24, 2023
• Last Verified: March 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: 0702-032

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