This is a single center, open-label phase 1 study to assess the safety and feasibility of PSMA-specific CAR modified autologous T cells (CART-PSMA cells) in patients with advanced prostate cancer.
Part A (Dose Escalation) + Part B (Expansion Cohort) total up to 20 patients enrolled.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
This study consists of 2 parts: Part A (Dose Escalation): The investigators are looking the highest dose of the study intervention that can be administered safely without severe or unmanageable side effects in participants that advanced prostate cancer. Part B (Expansion Cohort): Participants will be treated at the respective dose (at or below the Maximum Tolerated Dose), as determined during Part A (Dose Escalation). Up to 4 dosing cohorts, with up to 3 subjects enrolled in each cohort, will be explored as follows: Cohort 1: CART-PSMA cells 1-3x10\^7/M\^2 (body surface area); Cohort 2: CART-PSMA cells 1-3x10\^8/M\^2 (body surface area); Cohort 3: Lymphodepletion chemotherapy + CART-PSMA cells 1-3x10\^7/M\^2 (body surface area); Cohort 4: Lymphodepletion chemotherapy + CART-PSMA cells 1-3x10\^8/M\^2 (body surface area).
Chinese PLA General Hospital
Beijing, China
RECRUITINGOccurrence of study related adverse events, laboratory toxicities and clinical events that are possibly, likely, or definitely related to study participation.
Assessing the type, frequency, severity, and duration of adverse events as a result of CART-PSMA cell infusion via physical, laboratory and imaging examination.
Time frame: Up to 15 years
The persistence, accumulation, and migration of CART-PSMA cells.
Assessing the trafficking of CART-PSMA cells in the peripheral blood by quantifying the mRNA of CAR gene at the time of each infusion as well as at each time of follow-up blood collection. Peripheral blood will be collected prior to the initial infusion and will be set as baseline.
Time frame: Up to 2 years
Overall survival (OS)
Estimating median OS from CART-PSMA cell infusion to the event date (death) or last contact date (censor date) by Kaplan Meier methods.
Time frame: Up to 15 years
Progression-free survival (PFS)
Estimating median PFS by survival without biochemical (PSA) or radiographic evidence of disease progression or relapse from CART-PSMA cell infusion to event date (progression/relapse or death); the censor date: off protocol therapy date (required disallowed treatment or withdrawal of consent for further therapy) or last contact date.
Time frame: Up to 15 years
Patterns of change in PSA (prostate-specific antigen)
Assessing PSA response by the percentage of change in PSA from baseline to the defined time-frame on therapy (or earlier if patients discontinue therapy prior to the time-frame) as well as the maximum decline in PSA that occurs at any point during CART-PSMA cell infusion.
Time frame: Up to 5 years
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Serum cytokine profile
Assessing potential cytokine release syndrome (CRS) toxicity and CART cell effector function, sequential serum samples by analysis of Th1/Th2 cytokines (e.g., IL-2, IFNgamma, TNFalpha, IL-10, GMCSF, IL-6, MIP-1alpha) before and after CART-PSMA cell infusion.
Time frame: Up to 2 years
Phenotypes and frequencies of immune cell subsets in the peripheral blood pre- and post-therapy
Assessing phenotypes and frequencies of immune cell subsets in the peripheral blood, T cell subsets and phenotypes utilising groups of labelled antibodies.
Time frame: Up to 2 years
Changes in circulating tumor cells in peripheral blood
Assessing changes in levels of circulating tumor cells (CTC) to investigate if decreases in CTC levels correlate with response.
Time frame: Up to 2 years
Circulating cell-free deoxyribonucleic acid (cfDNA) in peripheral blood
Assessing changes in levels of cfDNA to investigate if decreases in cfDNA levels correlate with response.
Time frame: Up to 2 years