LIGHT-PSMA-CART in Treating Patients With Castrate-Resistant Prostate Cancer

NCT ID: NCT04053062

Last Updated: 2024-01-05

Basic Information

• Recruitment Status: SUSPENDED
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-16
• Study Completion Date: 2024-10-15

Brief Summary

This is a single center, single arm Phase I study to establish the safety and efficacy of intravenously administered lentivirally transduced LIGHT-PSMA-specific CAR modified autologous T cells (PSMA-CART cells) in patients with CRPC.

Detailed Description

This is a Phase I study evaluating the safety and efficacy of PSMA targeting autologous CAR T cells co-expressing LIGHT in a 3+3 dose escalation design. Cohort 1 subjects (N=3 or 6) will receive a tolal dose of 3x 10^6/kg body weight (KgBW) LIGHT-PSMA-CART cells at split doses after a conditioning chemotherapeutic regimen(Cy+Flu). If 1 DLT/3 subjects occurs, the study will enroll an additional 3 subjects at this dose level. If 0 DLT/3 subjects or 1 DLT/6 subjects occurs, the study will advance to Cohort 2, with a total dose of 6 x 10^6/ KgBW.

Conditions

Castrate-Resistant Prostate Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

LIGHT-PSMA-CART

Patients undergo leukapheresis. Patients then receive cyclophosphamide and fludarabine on days -6 to -4. Patients receive LIGH-PSMA-CART IV at split doses from day 0 on.

Group Type: EXPERIMENTAL

LIGHT-PSMA-CART cells

Intervention Type: BIOLOGICAL

LIGHT-PSMA-CART cells will be given IV at split doses

Interventions

LIGHT-PSMA-CART cells

LIGHT-PSMA-CART cells will be given IV at split doses

Intervention Type: BIOLOGICAL

Other Intervention Names

Autologous PSMA-specific chimeric antigen cells co-expressing LIGHT

Eligibility Criteria

Inclusion Criteria

• Fully understand and voluntarily sign informed consent.
• Male, aged 18 to 75 years old.
• Expected survival > 6 months.
• CRPC patients: Prostate cancer is still progressing after continuous androgen deprivation therapy. Including, castrate levels of serum testosterone (<50ng/dl or <1.7nmol/L); or prostate specific antigen (PSA) increased more than 50% at intervals of one week or three consecutive times, and PSA>1 ug/L; or imaging scans revealed two or more new lesions or enlargement of soft tissue lesions that met the criteria for evaluating solid tumor response.
• CRPC patients received abiraterone or chemotherapy for 3 months or more, and were ineffective or progressive (PSA continued to rise for 3 months, or bone scan/whole-body MRI/PET-CT showed local recurrence or new metastasis).
• Immunohistochemical staining of repetitive biopsy tissues showed the expression of PSMA in tumor cells was more than 50%.
• ECOG score <2.
• Hgb > 10 g/dl.
• PLT > 100×109/L.
• ANC > 1.5×109/L.

Exclusion Criteria

• Prior treatment with any immunotherapy, including CART therapy, tumor vaccine therapy, radium-223, checkpoint inhibitors.
• Prior treatment with any PSMA targeting therapy.
• Subjects with severe mental disorders.
• Subjects with severe cardiovascular diseases: a, New York Heart Association (NYHA) stage III or IV congestive heart failure; b, history of myocardial infarction or coronary artery bypass grafting (CABG) within 6 months; c, clinical significance of ventricular arrhythmia, or history of unexplained syncope, non-vasovagal or dehydration; d, history of severe non-ischemic cardiomyopathy; e, the left ventricular ejection fraction (LVEF < 55%) was decreased by echocardiography or MUGA scan (within 8 weeks before PBMC collection), and abnormal interventricular septal thickness and atrioventricular size associated with myocardial amyloidosis.
• Patients with ongoing or active infection.
• Aspartate aminotransferase or Alanine aminotransferase >2.5*ULN; CK>1.5*ULN; CK-MB>1.5*ULN; TnT>1.5*ULN.
• Total bilirubin >1.5*ULN.
• Partial prothrombin time or activated partial thromboplastin time or international standardized ratio > 1.5*ULN without anticoagulant treatment.
• History of participation in other clinical studies within 3 months or treatment with any gene therapy product.
• Intolerant or allergic to cyclophosphamide or fludarabine.
• Subjects not appropriate to participate in this clinical study judged by investigators.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Changhai Hospital

OTHER

Sponsor Role: collaborator

Bioray Laboratories

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Shancheng Ren, Professor

Role: PRINCIPAL_INVESTIGATOR

Changhai Hospital

Locations

Changhai Hospital

Shanghai, Shanghai Municipality, China

Countries

China

Other Identifiers

2020-CAR-00CH1

Identifier Type: -

Identifier Source: org_study_id