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

Relapsed/Refractory Large B-Cell Lymphoma Clinical Trial

— ELEVATION  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05800977
• Other study ID #: 0702-032
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: February 22, 2023
• Est. completion date: March 31, 2027

Study information

• Verified date: March 2023
• Source: Cellular Biomedicine Group Ltd.
• Contact: Yuqin Song, M.D., PhD
• Phone: 86-10-88196116
• Email: SongYQ_VIP[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 72
• Est. completion date: March 31, 2027
• Est. primary completion date: March 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Relapsed/Refractory Large B-Cell Lymphoma

Intervention

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

Locations

Country	Name	City	State
China	Peking Cancer Hospital	Beijing
China	The First Affiliated Hospital, Zhejiang University School of Medicine	Hangzhou

Sponsors (1)

Lead Sponsor	Collaborator
Cellular Biomedicine Group Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Phase 1b: Recommended Phase 2 Dose (R2PD)	Based on DLTs rates and overall safety profile	Up to 2 years after C-CAR039 infusion
Primary	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	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
Secondary	Phase 2: Incidence and Severity of Adverse Events (AEs)	Incidence and severity of any AEs	Up to 2 years after C-CAR039 infusion
Secondary	ORR	Best response, including PR and CR	Up to 2 years after C-CAR039 infusion
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Maximal plasma concentration (Cmax)	Maximal plasma concentration of C-CAR039 in peripheral blood	Up to 2 years after C-CAR039 infusion
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Anti-drug (C-CAR039) antibody	Presence of serum anti-drug (C-CAR039) antibody	Up to 2 years after C-CAR039 infusion