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

• Sponsor: Cellular Biomedicine Group Ltd. (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT05800977
• Collaborator: (none)
• Enrollment: 72
• Locations: 2
• Arm: 1
• Anticipated Duration (Months): 49.2
• Patients Per Site: 36
• Patients Per Site Per Month: 0.7

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Relapsed/Refractory Large B-Cell Lymphoma	Biological: Prizloncabtagene autoleucel	Phase 1/Phase 2

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 72 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Feb 22, 2023
• Anticipated Primary Completion Date: Mar 31, 2027
• Anticipated Study Completion Date: Mar 31, 2027

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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)

2. Phase 1b: Recommended Phase 2 Dose (R2PD) [Up to 2 years after C-CAR039 infusion]

   Based on DLTs rates and overall safety profile

3. 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

1. 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

2. Phase 2: Incidence and Severity of Adverse Events (AEs) [Up to 2 years after C-CAR039 infusion]

   Incidence and severity of any AEs

3. ORR [Up to 2 years after C-CAR039 infusion]

   Best response, including PR and CR

4. 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

5. 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

6. 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

7. 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

8. 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

9. Maximal plasma concentration (Cmax) [Up to 2 years after C-CAR039 infusion]

   Maximal plasma concentration of C-CAR039 in peripheral blood

10. 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

11. 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

12. 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

13. 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

14. Anti-drug (C-CAR039) antibody [Up to 2 years after C-CAR039 infusion]

    Presence of serum anti-drug (C-CAR039) antibody

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Peking Cancer Hospital	Beijing		China
2	The First Affiliated Hospital, Zhejiang University School of Medicine	Hangzhou		China

Sponsors and Collaborators

• Cellular Biomedicine Group Ltd.

Investigators

• Principal Investigator: Yuqin Song, M.D., PhD, Peking Cancer Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Cellular Biomedicine Group Ltd.
• ClinicalTrials.gov Identifier: NCT05800977
• Other Study ID Numbers: 0702-032
• First Posted: Apr 6, 2023
• Last Update Posted: Apr 6, 2023
• Last Verified: Mar 1, 2023

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Lymphoma; Lymphoma, B-Cell

Study Results

No Results Posted as of Apr 6, 2023