Relapsed/Refractory Large B-Cell Lymphoma
Conditions
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.
Interventions
BIOLOGICALPrizloncabtagene autoleucel
Prizlon-cel is a novel 2nd generation 4-1BB bispecific chimeric antigen receptor T-cell (CAR-T) targeting both CD19 and CD20 antigens
Sponsors
Shanghai AbelZeta Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1b: Incidence and Severity of Treatment-emergent Adverse Events (TEAEs) | Up to 90 days after C-CAR039 infusion | Incidence and severity of TEAEs , including dose limiting toxicities (DLTs) |
| Phase 1b: Recommended Phase 2 Dose (R2PD) | Up to 3 months after C-CAR039 infusion | Based on DLTs rates and overall safety profile |
| 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
| Measure | Time frame | Description |
|---|---|---|
| ORR | Up to 2 years after C-CAR039 infusion | Best response, including PR and CR |
| 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 |
| 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 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 |
| 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 |
| Phase 1b: Incidence and Severity of Adverse Events (AEs) | Up to 2 years after C-CAR039 infusion | Incidence and severity of AEs |
| 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 |
| 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 |
| 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 |
| 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 |
| Anti-drug (C-CAR039) antibody | Up to 2 years after C-CAR039 infusion | Presence of serum anti-drug (C-CAR039) antibody |
| 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 |
| Phase 2: Incidence and Severity of Adverse Events (AEs) | Up to 2 years after C-CAR039 infusion | Incidence and severity of any AEs |
Countries
China
Contacts
Primary ContactWeili Zhao, M.D., PhD
Backup ContactLugui Qiu, M.D., PhD
Outcome results
None listed