Clinical trial NCT05800977: A Study of C-CAR039 (Prizloncabtagene Autoleucel) in Patients with Relapsed/Refractory Large B-Cell Lymphoma
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Relapsed/Refractory Large B-Cell Lymphoma
Lead sponsor: Shanghai AbelZeta Ltd.
Sponsor class: INDUSTRY
First posted: 2023-04-06
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Phase 1b: Incidence and Severity of Adverse Events (AEs)
timeFrame: Up to 2 years after C-CAR039 infusion
measure: Phase 1b: Recommended Phase 2 Dose (R2PD)
timeFrame: Up to 2 years after C-CAR039 infusion
measure: Phase 2: Overall Response Rate (ORR) at 3 months
timeFrame: Up to 3 months after C-CAR039 infusion
Secondary outcomes:
measure: Phase 1b: ORR at 3 months
timeFrame: Up to 3 months after C-CAR039 infusion
measure: Phase 2: Incidence and Severity of Adverse Events (AEs)
timeFrame: Up to 2 years after C-CAR039 infusion
measure: ORR
timeFrame: Up to 2 years after C-CAR039 infusion
measure: ORR at 6 months
timeFrame: Up to 6 months after C-CAR039 infusion
measure: Duration of response (DOR)
timeFrame: Up to 2 years after C-CAR039 infusion
measure: Time to response (TTR)
timeFrame: Up to 2 years after C-CAR039 infusion
measure: Progression-free survival (PFS)
timeFrame: Up to 2 years after C-CAR039 infusion
measure: Overall survival (OS)
timeFrame: Up to 2 years after C-CAR039 infusion
measure: Maximal plasma concentration (Cmax)
timeFrame: Up to 2 years after C-CAR039 infusion
measure: Time to reach the maximal plasma concentration (Tmax)
timeFrame: Up to 2 years after C-CAR039 infusion
measure: Area under the curve within 28 days (AUC0-28d)
timeFrame: Up to 28 days after C-CAR039 infusion
measure: Time of last measurable observed concentration (Tlast)
timeFrame: Up to 2 years after C-CAR039 infusion
measure: The B cell percentage changes and CD19/CD20 expression changes in blood
timeFrame: Up to 2 years after C-CAR039 infusion
measure: Anti-drug (C-CAR039) antibody
timeFrame: Up to 2 years after C-CAR039 infusion
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Beijing
country: China
facility: Beijing GoBroad Hospital
city: Beijing
country: China
facility: Peking University Third Hospital
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
city: Guangzhou
country: China
facility: Zhujiang Hospital of Southern Medical University
city: Hangzhou
country: China
facility: The First Affiliated Hospital Zhejiang University School of Medicine
city: Jinan
country: China
facility: Cancer Hospital of Shandong First Medical University
city: Nanchang
country: China
facility: Jiangxi Cancer Hospital
city: Nanjing
country: China
facility: Jiangsu Province Hospital
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiaotong University School of Medicine
city: Tianjin
country: China
facility: Chinese Academy of Medical Sciences Hematology Hospital
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute& Hospital
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
Study officials:
affiliation: Ruijin Hospital
name: Weili Zhao, M.D., PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chinese Academy of Medical Sciences Hematology Hospital
name: Lugui Qiu
role: PRINCIPAL_INVESTIGATOR
References: