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

Sponsors and Collaborators:	Roger Williams Medical Center Department of Defense
Information provided by:	Roger Williams Medical Center
ClinicalTrials.gov Identifier:	NCT00664196

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 I

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Dose Comparison, Single Group Assignment, Safety/Efficacy Study
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:

MedlinePlus related topics: Cancer Prostate Cancer

U.S. FDA Resources

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:	April 2010
Estimated Primary Completion Date:	April 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental	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.

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 phlebotomy or leukopheresis, transported to the RWMC cGMP Cell Manipulation Core and transduced with retrovirus containing a chimeric immune receptor (CIR) that is expressed on the modified cells. This CIR 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 in a dose escalation of 10^9 to 10^11 cells following 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:

Histologically confirmed diagnosis of prostate cancer
Tumor is hormone refractory
Elevated PSA
Bone Scan positive for metastatic prostate cancer
Life expectancy > 4 months
Performance status 0-1
WBC > 4.0
Platelets > 100,000
Hemoglobin > 8.0
Creatinine < 1.5mg/dl
Direct Bilirubin < 1.5 mg/dl
No evidence of CHF, CAD, cardiac arrhythmias, A-fib, A flutter, myocardial infarction.
No serious, symptomatic obstructive or emphysematous lung disease
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
Patients must have a biopsy able tumor, and be willing to undergo biopsy (Group 3 only)
Patient is at least 18 years of age.

Exclusion Criteria:

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

Contacts and Locations

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

Contacts

Contact: Robin A Davies, BA, BSN, RN

401-456-2268

rdavies@rwmc.org

Locations

United States, Rhode Island
Roger Williams Hospital	Recruiting
Providence, Rhode Island, United States, 02908
Contact: Robin A Davies, BA, BSN, RN 401-456-2268 rdavies@rwmc.org
Principal Investigator: Richard P Junghans, PhD, MD

Sponsors and Collaborators

Roger Williams Medical Center

Department of Defense

Investigators

Principal Investigator:

Richard P Junghans, PhD, MD

Roger Williams Hospital

More Information

No publications provided

Responsible Party:	Roger Williams Medical Center ( Richard P. Junghans, PhD, MD; Principal Investigator )
Study ID Numbers:	595-04, W81XWH-05-1-0408
Study First Received:	April 17, 2008
Last Updated:	May 1, 2008
ClinicalTrials.gov Identifier:	NCT00664196 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Roger Williams Medical Center:

Prostate Cancer
T cells
Gene Transfer

Study placed in the following topic categories:

Prostatic Diseases
Genital Neoplasms, Male
Urogenital Neoplasms

Genital Diseases, Male
Hormones
Prostatic Neoplasms

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Site
Prostatic Diseases
Genital Neoplasms, Male

Urogenital Neoplasms
Genital Diseases, Male
Prostatic Neoplasms

ClinicalTrials.gov processed this record on September 11, 2009