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A Study of CART-PSMA-TGFβRDN in Patients With Metastatic Castration Resistant Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04227275
Recruitment Status : Active, not recruiting
First Posted : January 13, 2020
Last Update Posted : May 13, 2021
Sponsor:
Information provided by (Responsible Party):
Tmunity Therapeutics

Brief Summary:
Multi-center, open-label, Phase 1 study of the safety, tolerability and feasibility of dosing patients harboring metastatic castration resistant prostate cancer (mCRPC) with genetically modified autologous T cells (CART-PSMA-TGFβRDN cells) engineered to express a chimeric antigen receptor (CAR) capable of recognizing the tumor antigen prostate-specific membrane antigen (PSMA) and activating the T cell.

Condition or disease Intervention/treatment Phase
Metastatic Castration-resistant Prostate Cancer Biological: CART-PSMA-TGFβRDN Drug: Cyclophosphamide Drug: Fludarabine Drug: Anakinra Phase 1

Detailed Description:

This is a Phase 1 single-arm study designed to identify the dose and regimen of CART-PSMA- TGFβRDN cells that can be safely administered intravenously following the lymphodepletion (LD) regimen to patients with metastatic castration resistant prostate cancer (mCRPC). Following Dose Escalation, a Cohort Expansion will enroll patients to further explore the safety and tolerability of the selected dose and schedule.

It is anticipated that up to 50 patients will enroll in this study in both dose escalation and cohort expansion.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description: Sequential dose escalation
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Open-Label, Multi-Center Study of PSMA Targeted Genetically Modified Chimeric Antigen Receptor T Cells in Patients With Metastatic Castration Resistant Prostate Cancer
Actual Study Start Date : November 22, 2019
Estimated Primary Completion Date : November 30, 2022
Estimated Study Completion Date : November 30, 2036

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: Dose Escalation
Dose escalation of intravenous CART-PSMA-TGFβRDN cells for patients with metastatic castration resistant prostate cancer
Biological: CART-PSMA-TGFβRDN
Intravenous administration of genetically modified autologous T cells engineered to express a protein capable of recognizing the tumor antigen prostate-specific membrane antigen (PSMA), as well as a dominant negative TGFβ receptor

Drug: Cyclophosphamide
Patients will receive cyclophosphamide and fludarabine lymphodepletion chemotherapy followed by the investigational product, CART-PSMA-TGFβRDN genetically modified T cells

Drug: Fludarabine
Patients will receive cyclophosphamide and fludarabine lymphodepletion chemotherapy followed by the investigational product, CART-PSMA-TGFβRDN genetically modified T cells

Drug: Anakinra
In applicable cohorts, patients will receive anakinra prophylactically starting on the day of administration of investigational product, CART-PSMA-TGFβRDN genetically modified T cells




Primary Outcome Measures :
  1. Dose Escalation: Dose Identification of CART-PSMA-TGFβRDN [ Time Frame: Up to 2 years ]
    Incidence of Dose Limiting Toxicity (DLT)

  2. Cohort Expansion: Safety of CART-PSMA-TGFβRDN [ Time Frame: Up to 2 years ]
    Percentage of patients experiencing adverse events (AEs), including serious and severe AEs overall, by dose level, and severity grade


Secondary Outcome Measures :
  1. Preliminary efficacy of CART-PSMA-TGFβRDN as assessed by biochemical Objective Response Rate (ORR) [ Time Frame: Up to 2 years ]
    ORR defined as the proportion of patients with maximal prostate-specific antigen (PSA) decline of greater than or equal to 50% at 12 weeks post infusion

  2. Feasibility of CART-PSMA-TGFβRDN [ Time Frame: Up to 2 years ]
    Proportion of patients who did not receive CART-PSMA-TGFβRDN cells

  3. Peripheral expansion and persistence of CART-PSMA-TGFβRDN [ Time Frame: Up to 15 years ]
    Quantitative polymerase chain reaction (qPCR)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed histologic diagnosis of prostate cancer and have mCRPC, with castrate levels of testosterone (<50 ng/mL)
  • PSA measurable disease per Prostate Working Group 3 (PCWG3) criteria
  • Prior therapies defined as at least 2 prior lines of systemic therapy for prostate cancer, including at least one second generation androgen receptor inhibitor and/or CYP17α inhibitor. At least one line of prior therapy must be in the mCRPC setting
  • Estimated estimated glomerular filtration rate ≥ 60 mL/min by Modification of Diet in Renal Disease criteria
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5x the upper limit of normal (ULN); patients with hepatic metastases ALT and AST ≤ 3.0 x ULN
  • Serum total bilirubin < 1.5 mg/dL unless patient has known Gilbert's Syndrome, then serum bilirubin ≤3 mg/dL
  • Serum albumin ≥ 3.0 g/dL
  • Left ventricular ejection fraction (LVEF) ≥ 50%. LVEF assessment must have been performed within 8 weeks of enrollment
  • Hemoglobin ≥ 8 g/dL
  • Absolute neutrophil count ≥ 1000/μL
  • Platelet count ≥ 75,000/μL
  • Patients who have not undergone bilateral orchiectomy must be able to continue gonadotropin-releasing hormone (GnRH) therapy during the study
  • Eastern Cooperative Oncology Group (ECOG) score of 0 or 1
  • Toxicities from any previous therapy must have recovered to Grade 1 or baseline
  • Patients of reproductive potential agree to use of approved highly effective contraceptive methods

Exclusion Criteria:

  • Active invasive cancer, other than the proposed cancer included in the study, within 2 years prior to screening, unless treated with curative intent
  • Current treatment with systemic corticosteroids (defined as a dose greater than the equivalent of prednisone 10 mg/day)
  • Active autoimmune disease (including connective tissue disease, uveitis, sarcoidosis, inflammatory bowel disease or multiple sclerosis) or a history of severe autoimmune disease requiring prolonged immunosuppressive therapy (any immunosuppressive therapy within 6 weeks prior to screening visit)
  • Current human immunodeficiency virus (HIV), hepatitis C virus, hepatitis B virus infections; Patients who are hepatitis B core antigen positive, hepatitis B surface antigen negative, should have a quantitative viral load measured; If viral load is undetectable, the patient will not be excluded if hey are able to be treated with anti-viral medication for at least 7 days prior to lymphodepletion until at least 6 months after infusion with viral load and ALT monitoring
  • Active or uncontrolled medical or psychological condition that would preclude participation
  • History of seizure disorder
  • Prior allogeneic stem cell transplant
  • Central nervous system malignancy
  • History of severe infusion reaction to monoclonal antibodies or biological therapies, or to study product excipients that would preclude the patient safely receiving CART-PSMA-TGFβRDN cells
  • History of being previously treated with a J591 antibody-based therapy
  • Ferritin levels ≥ 4x the upper limit of normal prior to apheresis or prior to the start of lymphodepleting chemotherapy
  • Active or recent (within the past 6 months prior to apheresis or lymphodepletion) cardiovascular disease, defined as (1) New York Heart Association Class III or IV heart failure, (2) unstable angina, (3) a history of recent (within 6 months) myocardial infarction or sustained (> 30 second) ventricular tachyarrhythmias, or (4) cerebrovascular accident
  • Any active infection currently being treated or any infection within the last 6 weeks that required 7 days or more of IV antibiotics or any active infection within the last 4 weeks that requires use of oral antibiotics. Patients may be eligible once these timeframes elapse and with evidence that the infection has completely resolved
  • Have inadequate venous access for or contraindications for the apheresis procedure
  • Must agree not to participate in a conception process or must agree to a highly effective method of contraception

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04227275


Locations
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United States, Florida
Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Kansas
The University of Kansas Hospital
Kansas City, Kansas, United States, 66160
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15232
United States, Tennessee
Sarah Cannon Research Insitute
Nashville, Tennessee, United States, 37203
United States, Washington
University of Washington Medical Center
Seattle, Washington, United States, 98195
Sponsors and Collaborators
Tmunity Therapeutics
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Responsible Party: Tmunity Therapeutics
ClinicalTrials.gov Identifier: NCT04227275    
Other Study ID Numbers: CART-PSMA-TGFβRDN-02
First Posted: January 13, 2020    Key Record Dates
Last Update Posted: May 13, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Tmunity Therapeutics:
Chimeric Antigen Receptor (CAR)
T-cells
Prostate-Specific Membrane Antigen (PSMA)
Prostate Cancer
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Cyclophosphamide
Fludarabine
Interleukin 1 Receptor Antagonist Protein
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists