CART-PSMA Cells for Advanced Prostate Cancer

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

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.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: CART-PSMA cells

Detailed Description

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

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jay Zhang, MD/PhD; Phone Number: 858-205-4558; Email: jiezhang8@hotmail.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Chinese PLA General Hospital
    • Contact: Jay Zhang, MD/PhD
    • Principal Investigator: Xu Zhang, MD/PhD
    • Sub-Investigator: Haixing Mai, MD/PhD
    • Sub-Investigator: Yu Gao, MD/PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 31 years to 81 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. All participants must have the ability to understand and the willingness to sign a written informed consent.
2. Histologic confirmation of prostate cancer.
3. Tumor expressing PSMA as demonstrated by immunohistochemistry analysis or other methods.
4. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2.
5. Under general air conditions, blood oxygen saturation >90%.
6. 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.
7. Adequate renal function, specifically serum creatinine < 2.0 mg/dl.
8. Adequate cardiac function, specifically left ventricular ejection fraction (LVEF)≥50%.
9. Hemoglobin concentration ≥80g/L.
10. 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:

1. Patients with other malignant tumors or major diseases.
2. Patients who are already undergoing other clinical drug trials or other gene therapy or cell therapy.
3. Patients with uncontrolled active infection.
4. Patients with active hepatitis B or hepatitis C infection.
5. Patients with human immunodeficiency virus (HIV) infection.
6. Patients who are being treated with immunosuppressive agents or systemic steroids (other than inhalation therapy).
7. Patients with various types of serious heart disease or a history of severe cerebrovascular disease.
8. Patients with congenital immune deficiency diseases or bone marrow deficiency diseases.
9. 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.
10. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: autologous CART-PSMA cells; Cohort 1： CART-PSMA cells 1-3x10^7/M^2(body surface area) on Day 0; Cohort 2： CART-PSMA cells 1-3x10^8/M^2(body surface area) on Day 0; Cohort 3： Lymphodepletion chemotherapy with fludarabine (30 mg/m2 body surface area) plus cyclophosphamide (300 mg/m2 body surface area) for 3 consecutive days during D-7 to D-3, followed by the infusion of CART-PSMA cells at 1-3x10^7/M^2(body surface area) on Day 0. Cohort 4： Lymphodepletion chemotherapy with fludarabine (30 mg/m2 body surface area) plus cyclophosphamide (300 mg/m2 body surface area) for 3 consecutive days during D-7 to D-3, followed by the infusion of CART-PSMA cells at 1-3x10^8/M^2(body surface area) on Day 0.

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 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).; Other Names: No other names

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence 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.	Up to 15 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	Up to 5 years
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.	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.	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.	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.	Up to 2 years

Collaborators and Investigators

• Sponsor: Nova Therapeutics LLC
• Collaborators: Chinese PLA General Hospital
• Investigators: Study Director: Jay Zhang, Nova Therapeutics LLC

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2023
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: December 1, 2022
• First Submitted That Met QC Criteria: December 12, 2022
• First Posted (Actual): December 19, 2022

Study Record Updates

• Last Update Posted (Actual): November 15, 2024
• Last Update Submitted That Met QC Criteria: November 13, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: NT1921-H301-CART-PSMA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No