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

Primary Purpose

Castrate-Resistant Prostate Cancer

Status
Suspended
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
LIGHT-PSMA-CART cells
Sponsored by
Bioray Laboratories
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Castrate-Resistant Prostate Cancer focused on measuring Castrate-Resistant

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)MaleDoes not accept healthy volunteers

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.

Sites / Locations

  • Changhai Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

LIGHT-PSMA-CART

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

PSA response rate
proportion of patients with ≥50% PSA decline from baseline at any time point after therapy and maintained for ≥4 weeks
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.
Duration time of CART cells in vivo
Number of persistent PSMA-CART cells detected by Q-PCR or flow cytometry

Full Information

First Posted
August 8, 2019
Last Updated
January 25, 2023
Sponsor
Bioray Laboratories
Collaborators
Changhai Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04053062
Brief Title
LIGHT-PSMA-CART in Treating Patients With Castrate-Resistant Prostate Cancer
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)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Suspended
Why Stopped
Due to efficacy evaluation
Study Start Date
July 16, 2020 (Actual)
Primary Completion Date
November 15, 2023 (Anticipated)
Study Completion Date
December 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bioray Laboratories
Collaborators
Changhai Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Castrate-Resistant Prostate Cancer
Keywords
Castrate-Resistant

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
3 x 10^6/ KgBW; 6 x 10^6/ KgBW
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
LIGHT-PSMA-CART
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
LIGHT-PSMA-CART cells
Other Intervention Name(s)
Autologous PSMA-specific chimeric antigen cells co-expressing LIGHT
Intervention Description
LIGHT-PSMA-CART cells will be given IV at split doses
Primary Outcome Measure Information:
Title
Incidence of toxicity graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03
Description
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.
Time Frame
28 days
Secondary Outcome Measure Information:
Title
PSA response rate
Description
proportion of patients with ≥50% PSA decline from baseline at any time point after therapy and maintained for ≥4 weeks
Time Frame
24 weeks
Title
Radiographic response rate by RECIST 1.1 & PCWG3.
Description
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.
Time Frame
24 weeks
Title
Duration time of CART cells in vivo
Description
Number of persistent PSMA-CART cells detected by Q-PCR or flow cytometry
Time Frame
24 weeks

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shancheng Ren, Professor
Organizational Affiliation
Changhai Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Changhai Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200433
Country
China

12. IPD Sharing Statement

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

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