Phase Ia/Ib Trial of Anti-PSMA Designer T Cells in Advanced Prostate Cancer After Non-Myeloablative Conditioning
18 Years
N/A
Male
Prostate Cancer
Trial Information
Phase Ia/Ib Trial of Anti-PSMA Designer T Cells in Advanced Prostate Cancer After Non-Myeloablative Conditioning
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.
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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
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)
Outcome Time Frame:
1 Month
Safety Issue:
Yes
Principal Investigator
Richard P Junghans, PhD, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Roger Williams Hospital
Authority:
United States: Food and Drug Administration
Study ID:
595-04
NCT ID:
NCT00664196
Start Date:
April 2008
Completion Date:
July 2016
Related Keywords:
- Prostate Cancer
- Prostate Cancer
- T cells
- Gene Transfer
- Prostatic Neoplasms
Name | Location |
|---|---|
| Roger Williams Medical Center | Providence, Rhode Island 02908-4735 |
