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

Castrate-Resistant Prostate Cancer Clinical Trial

Official title:

A Phase I Study to Evaluate the Safety and Efficacy of PSMA-CART Co-expressing LIGHT in Treating Patients With Castrate-Resistant Prostate Cancer (CRPC)

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT04053062
• Other study ID #: 2020-CAR-00CH1
• Status: Suspended
• Phase: Phase 1
• Start date: July 16, 2020
• Est. completion date: October 15, 2024

Study information

• Verified date: January 2024
• Source: Bioray Laboratories
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 12
• Est. completion date: October 15, 2024
• Est. primary completion date: May 15, 2022
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 75 Years

Eligibility

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: Subjects who meet any of the following exclusion criteria will be excluded

• 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.

Related Conditions & MeSH terms

• Castrate-Resistant Prostate Cancer
• Prostatic Neoplasms

Intervention

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

Locations

Country	Name	City	State
China	Changhai Hospital	Shanghai	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Bioray Laboratories	Changhai Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of toxicity graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03	All adverse events (AEs) will be listed and summarized. Summaries of laboratory data will include, at a minimum, treatment-emergent laboratory abnormalities. Summaries of AEs and laboratory abnormalities will be based on the All Treated analysis set.	28 days
Secondary	PSA response rate	proportion of patients with =50% PSA decline from baseline at any time point after therapy and maintained for =4 weeks	24 weeks
Secondary	Radiographic response rate by RECIST 1.1 & PCWG3.	Proportion of patients with a best response of either complete response or partial response, assessed using Prostate Cancer Working group3(PCWG3) response criteria &RECIST 1.1.	24 weeks
Secondary	Duration time of CART cells in vivo	Number of persistent PSMA-CART cells detected by Q-PCR or flow cytometry	24 weeks