CART-PSMA Cells for Advanced Prostate Cancer
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: autologous CART-PSMA cells
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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).
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Outcome Measures
Primary Outcome Measures
- Occurrence of study related adverse events, laboratory toxicities and clinical events that are possibly, likely, or definitely related to study participation. [Up to 15 years]
Assessing the type, frequency, severity, and duration of adverse events as a result of CART-PSMA cell infusion via physical, laboratory and imaging examination.
Secondary Outcome Measures
- The persistence, accumulation, and migration of CART-PSMA cells. [Up to 2 years]
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.
- Overall survival (OS) [Up to 15 years]
Estimating median OS from CART-PSMA cell infusion to the event date (death) or last contact date (censor date) by Kaplan Meier methods.
- Progression-free survival (PFS) [Up to 15 years]
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.
- Patterns of change in PSA (prostate-specific antigen) [Up to 5 years]
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.
- Serum cytokine profile [Up to 2 years]
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.
- Phenotypes and frequencies of immune cell subsets in the peripheral blood pre- and post-therapy [Up to 2 years]
Assessing phenotypes and frequencies of immune cell subsets in the peripheral blood, T cell subsets and phenotypes utilising groups of labelled antibodies.
- Changes in circulating tumor cells in peripheral blood [Up to 2 years]
Assessing changes in levels of circulating tumor cells (CTC) to investigate if decreases in CTC levels correlate with response.
- Circulating cell-free deoxyribonucleic acid (cfDNA) in peripheral blood [Up to 2 years]
Assessing changes in levels of cfDNA to investigate if decreases in cfDNA levels correlate with response.
Eligibility Criteria
Criteria
Inclusion Criteria:
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All participants must have the ability to understand and the willingness to sign a written informed consent.
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Histologic confirmation of prostate cancer.
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Tumor expressing PSMA as demonstrated by immunohistochemistry analysis or other methods.
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Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2.
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Under general air conditions, blood oxygen saturation >90%.
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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.
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Adequate renal function, specifically serum creatinine < 2.0 mg/dl.
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Adequate cardiac function, specifically left ventricular ejection fraction (LVEF)≥50%.
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Hemoglobin concentration ≥80g/L.
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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:
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Patients with other malignant tumors or major diseases.
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Patients who are already undergoing other clinical drug trials or other gene therapy or cell therapy.
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Patients with uncontrolled active infection.
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Patients with active hepatitis B or hepatitis C infection.
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Patients with human immunodeficiency virus (HIV) infection.
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Patients who are being treated with immunosuppressive agents or systemic steroids (other than inhalation therapy).
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Patients with various types of serious heart disease or a history of severe cerebrovascular disease.
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Patients with congenital immune deficiency diseases or bone marrow deficiency diseases.
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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.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Chinese PLA General Hospital | Beijing | China |
Sponsors and Collaborators
- Nova Therapeutics LLC
- Chinese PLA General Hospital
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NT1921-H301-CART-PSMA