CART-PSMA Cells for Advanced Prostate Cancer

Prostate Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05656573
• Other study ID #: NT1921-H301-CART-PSMA
• Status: Recruiting
• Phase: Phase 1
• Start date: March 1, 2023
• Est. completion date: December 1, 2025

Study information

• Verified date: November 2023
• Source: Nova Therapeutics LLC
• Contact: Jay Zhang, MD/PhD
• Phone: 858-205-4558
• Email: jiezhang8[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 1, 2025
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 35 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

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. 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 on Day 0; cohort 2: CART-PSMA cells 1-3x10^8 on Day 0; cohort 3: CART-PSMA cells 1-3x10^7 on Day 0,following lymphodepleting chemotherapy with cyclophosphamide 300 mg/m2/day and fludarabine 30 mg/m2/day given over 3 days; cohort 4: CART-PSMA cells 1-3x10^8 on Day 0,following lymphodepleting chemotherapy with cyclophosphamide 300 mg/m2/day and fludarabine 30 mg/m2/day given over 3 days; 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).

Locations

Country	Name	City	State
China	Chinese PLA General Hospital	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Nova Therapeutics LLC	Chinese PLA General Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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