Castrate-Resistant Prostate Cancer
Conditions
Keywords
Castrate-Resistant
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.
Interventions
BIOLOGICALLIGHT-PSMA-CART cells
LIGHT-PSMA-CART cells will be given IV at split doses
Sponsors
Changhai Hospital
Bioray Laboratories
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
3 x 10\^6/ KgBW; 6 x 10\^6/ KgBW
Eligibility
Sex/Gender
MALE
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of toxicity graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 | 28 days | 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
| Measure | Time frame | Description |
|---|---|---|
| PSA response rate | 24 weeks | 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. | 24 weeks | 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 | 24 weeks | Number of persistent PSMA-CART cells detected by Q-PCR or flow cytometry |
Countries
China
Outcome results
None listed