Clinical trial NCT00664196: Trial of Anti-PSMA Designer T Cells in Advanced Prostate Cancer After Non-Myeloablative Conditioning
Official title: Phase Ia/Ib Trial of Anti-PSMA Designer T Cells in Advanced Prostate Cancer After Non-Myeloablative Conditioning
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE1
Conditions: Prostate Cancer
Keywords: Prostate Cancer
T cells
Gene Transfer
Lead sponsor: Roger Williams Medical Center
Sponsor class: OTHER
First posted: 2008-04-22
Enrollment: 18
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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 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

Primary outcomes:
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)
timeFrame: 1 Month
Secondary outcomes:
measure: Tumor Response
timeFrame: 1 Month
measure: Pharmacokinetics
timeFrame: 1 Month
measure: Pharmacodynamics
timeFrame: 1 Month
Other outcomes:
Locations:
city: Providence
country: United States
facility: Roger Williams Medical Center
state: Rhode Island
Study officials:
affiliation: Roger Williams Hospital
name: Richard P Junghans, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References: