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

NCT ID: NCT00664196

Last Updated: 2016-06-17

Basic Information

• Recruitment Status: SUSPENDED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-04-30
• Study Completion Date: 2018-12-31

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.

Conditions

Prostate Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Group Type: EXPERIMENTAL

Gene Modified T Cells

Intervention Type: BIOLOGICAL

One time infusion Modified T-Cells given through a vein in the arm or a catheter over a 30-60 minute period.

Interventions

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.

Intervention Type: BIOLOGICAL

Other Intervention Names

Designer T-Cells; PSMA; Hormone Refractory

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Roger Williams Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Richard P Junghans, PhD, MD

Role: PRINCIPAL_INVESTIGATOR

Roger Williams Hospital

Locations

Roger Williams Medical Center

Providence, Rhode Island, United States

Countries

United States

Other Identifiers

W81XWH-05-1-0408

Identifier Type: -

Identifier Source: secondary_id

595-04

Identifier Type: -

Identifier Source: org_study_id