Clinical trial NCT04053062: 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
Overall status: SUSPENDED
Phase: PHASE1
Conditions: Castrate-Resistant Prostate Cancer
Keywords: Castrate-Resistant
Lead sponsor: Bioray Laboratories
Sponsor class: INDUSTRY
Collaborators: name: Changhai Hospital
First posted: 2019-08-12
Enrollment: 12
Sex: MALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: 3 x 10\^6/ KgBW; 6 x 10\^6/ KgBW
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Incidence of toxicity graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03
timeFrame: 28 days
Secondary outcomes:
measure: PSA response rate
timeFrame: 24 weeks
measure: Radiographic response rate by RECIST 1.1 & PCWG3.
timeFrame: 24 weeks
measure: Duration time of CART cells in vivo
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Changhai Hospital
state: Shanghai
Study officials:
affiliation: Changhai Hospital
name: Shancheng Ren, Professor
role: PRINCIPAL_INVESTIGATOR
References: