CART-PSMA Cells for Advanced Prostate Cancer

Official title

Phase I Study of CART-PSMA Cells in Patients With Advanced Prostate Cancer

Overview

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.

Detailed description

Part A (Dose Escalation) + Part B (Expansion Cohort) total up to 20 patients enrolled.

Interventions

• Drug CART-PSMA cells
  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

Primary outcome measures

• Occurrence of study related adverse events, laboratory toxicities and clinical events that are possibly, likely, or definitely related to study participation. [Time frame: Up to 15 years]

Secondary outcome measures (8)

• The persistence, accumulation, and migration of CART-PSMA cells. [Time frame: Up to 2 years]
• Overall survival (OS) [Time frame: Up to 15 years]
• Progression-free survival (PFS) [Time frame: Up to 15 years]
• Patterns of change in PSA (prostate-specific antigen) [Time frame: Up to 5 years]
• Serum cytokine profile [Time frame: Up to 2 years]
• Phenotypes and frequencies of immune cell subsets in the peripheral blood pre- and post-therapy [Time frame: Up to 2 years]
• Changes in circulating tumor cells in peripheral blood [Time frame: Up to 2 years]
• Circulating cell-free deoxyribonucleic acid (cfDNA) in peripheral blood [Time frame: Up to 2 years]

Eligibility criteria

Inclusion criteria

• All participants must have the ability to understand and the willingness to sign a written informed consent.
• Histologic confirmation of prostate cancer.
• Tumor expressing PSMA as demonstrated by immunohistochemistry analysis or other methods.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2.
• Under general air conditions, blood oxygen saturation >90%.
• Adequate liver function, specifically alanine aminotransferase (ALT) < 3 times of upper limit of normal (ULN), aspartate transferase (AST)< 3 times of ULN, serum bilirubin and alkaline phosphatase < 2 times of ULN.
• Adequate renal function, specifically serum creatinine < 2.0 mg/dl.
• Adequate cardiac function, specifically left ventricular ejection fraction (LVEF)≥50%.
• Hemoglobin concentration ≥80g/L.
• The side effects brought by the latest treatment should be recovered, and the latest chemotherapy should be at least 7 days before; At least three t½ have passed since the latest immunotherapy.

Exclusion criteria

• Patients with other malignant tumors or major diseases.
• Patients who are already undergoing other clinical drug trials or other gene therapy or cell therapy.
• Patients with uncontrolled active infection.
• Patients with active hepatitis B or hepatitis C infection.
• Patients with human immunodeficiency virus (HIV) infection.
• Patients who are being treated with immunosuppressive agents or systemic steroids (other than inhalation therapy).
• Patients with various types of serious heart disease or a history of severe cerebrovascular disease.
• Patients with congenital immune deficiency diseases or bone marrow deficiency diseases.
• Patients with active autoimmune disease, including connective tissue disease, uveitis, inflammatory bowel disease, or multiple sclerosis; or a history of severe (as judged by the physician-investigator) autoimmune disease requiring prolonged immunosuppressive therapy.
• Patients with active medical condition that, in the opinion of the physician-investigator, would substantially increase the risk of uncontrollable CRS (cytokine release syndrome) or CAR Neurotoxicity.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Chinese PLA General Hospital — Beijing

Identifiers

NCT: NCT05656573 · NT1921-H301-CART-PSMA

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗