Trial of Anti-PSMA Designer T Cells in Advanced Prostate Cancer After Non-Myeloablative Conditioning

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2013 by Roger Williams Medical Center
Sponsor:
Information provided by (Responsible Party):
Roger Williams Medical Center
ClinicalTrials.gov Identifier:
NCT00664196
First received: April 17, 2008
Last updated: May 23, 2013
Last verified: May 2013
  Purpose

This study tests the safety and tolerability of autologous anti-PSMA gene-modified T cells (designer T cells) in hormone refractory prostate cancer.


Condition Intervention Phase
Prostate Cancer
Biological: Gene Modified T Cells
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase Ia/Ib Trial of Anti-PSMA Designer T Cells in Advanced Prostate Cancer After Non-Myeloablative Conditioning

Resource links provided by NLM:


Further study details as provided by Roger Williams Medical Center:

Primary Outcome Measures:
  • Determine the safety of using modified T cells by documenting the type and severity of any side effects and establishing the Maximum Tolerated Dose (MTD) [ Time Frame: 1 Month ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Tumor Response [ Time Frame: 1 Month ] [ Designated as safety issue: No ]
  • Pharmacokinetics [ Time Frame: 1 Month ] [ Designated as safety issue: No ]
  • Pharmacodynamics [ Time Frame: 1 Month ] [ Designated as safety issue: No ]

Estimated Enrollment: 18
Study Start Date: April 2008
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Biological: Gene Modified T Cells
One time infusion Modified T-Cells given through a vein in the arm or a catheter over a 30-60 minute period.
Other Names:
  • Designer T-Cells
  • PSMA
  • Hormone Refractory

Detailed Description:

The study creates autologous gene-modified T cells against prostate specific membrane antigen (PSMA, unrelated to PSA) (designer T cells) by ex vivo modification of patient T cells. T cells are collected by leukopheresis, transported to the RWMC cGMP Cell Manipulation Core and transduced with retrovirus containing a chimeric antigen receptor (CAR) that is expressed on the modified cells. This CAR links specificity of an antibody against PSMA with signaling domains of the T cell and redirects the recognition of the T cells to engage and kill prostate cancer cells anywhere in the body. These are administered at a dose of 10^10 with randomization to either low or moderate Interleukin 2 given by CI (continuous infusion) for one month following the T cell infusion. Subsequent subjects will receive 10^11 cells with Interleukin 2 at either low or moderate dose, in a non randomized manner, depending upon the outcome of the prior cohort. Prior to T cell infusion, all subjects will receive non-myeloablative (NMA) conditioning. This conditioning creates a "space" in the blood and marrow for engraftment of the infused cells to maintain of high level of anti-tumor effector T cells in the body. Each patient is treated with a single dose of T cells, without repeat dosing. Patients are followed for toxicity and response and pharmacokinetics-pharmacodynamics of the infused T cells. Patients are on-study for one-month after their T cell dose.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically confirmed diagnosis of prostate cancer
  2. Elevated PSA
  3. Life expectancy > 4 months
  4. Performance status 0-1
  5. ANC 1.0
  6. Platelets > 100,000
  7. Hemoglobin > 8.0
  8. Creatinine < 1.5mg/dl
  9. Direct Bilirubin < 1.5 mg/dl
  10. No evidence of CHF, CAD, cardiac arrhythmias, A-fib, A flutter, myocardial infarction.
  11. No serious, symptomatic obstructive or emphysematous lung disease
  12. No asthma requiring IV medication during last 12 months, no serious lung disease associated with dyspnea at normal activity levels, or at rest due to any cause, including cancer metastasis and pleural effusion
  13. Patients must have a biopsy able tumor, and be willing to undergo biopsy (Group 3 only)
  14. Patient is at least 18 years of age.

Exclusion Criteria:

  1. Serious or unstable renal, hepatic, pulmonary, cardiovascular, endocrine, rheumatologic or allergic disease based on history, labs or physical exam
  2. Active clinical disease caused by CMV, Hepatitis B, or C, HIV, TB
  3. Cytotoxic and/or radiation therapy during last 4 weeks prior to entry
  4. Any concurrent malignancies
  5. Patient requires systemic steroids
  6. Patient has participated in prior investigational therapy
  7. Patient has prior exposure to mouse antibody
  8. Patient has had irradiation to whole pelvis or >25% marrow
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00664196

Contacts
Contact: Robin A Davies, BA, BSN, RN 401-456-2419 rdavies@chartercare.org

Locations
United States, Rhode Island
Roger Williams Medical Center Recruiting
Providence, Rhode Island, United States, 02908
Contact: Robin A Davies, BA, BSN, RN    401-456-2419    rdavies@chartercare.org   
Principal Investigator: Richard P Junghans, PhD, MD         
Sponsors and Collaborators
Roger Williams Medical Center
Investigators
Principal Investigator: Richard P Junghans, PhD, MD Roger Williams Hospital
  More Information

No publications provided

Responsible Party: Roger Williams Medical Center
ClinicalTrials.gov Identifier: NCT00664196     History of Changes
Other Study ID Numbers: 595-04, W81XWH-05-1-0408
Study First Received: April 17, 2008
Last Updated: May 23, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Roger Williams Medical Center:
Prostate Cancer
T cells
Gene Transfer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases

ClinicalTrials.gov processed this record on August 19, 2014