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

Prostate Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT00664196
• Other study ID #: 595-04
• Secondary ID: W81XWH-05-1-0408
• Status: Suspended
• Phase: Phase 1
• First received: April 17, 2008
• Last updated: June 16, 2016
• Start date: April 2008
• Est. completion date: December 2018

Study information

• Verified date: June 2016
• Source: Roger Williams Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 18
• Est. completion date: December 2018
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

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.

Locations

Country	Name	City	State
United States	Roger Williams Medical Center	Providence	Rhode Island

Sponsors (1)

Lead Sponsor	Collaborator
Roger Williams Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)		1 Month	Yes
Secondary	Tumor Response		1 Month	No
Secondary	Pharmacokinetics		1 Month	No
Secondary	Pharmacodynamics		1 Month	No