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

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

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

Study Overview

• Status: Suspended
• Conditions: Prostate Cancer
• Intervention / Treatment: Biological: Gene Modified T Cells

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.

• Study Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Rhode Island
    • Providence, Rhode Island, United States, 02908
      • Roger Williams Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1	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.; Other Names: PSMA; Designer T-Cells; Hormone Refractory

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Time Frame
Tumor Response	1 Month
Pharmacokinetics	1 Month
Pharmacodynamics	1 Month

Collaborators and Investigators

• Sponsor: Roger Williams Medical Center
• Investigators: Principal Investigator: Richard P Junghans, PhD, MD, Roger Williams Hospital

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (ANTICIPATED): December 1, 2017
• Study Completion (ANTICIPATED): December 1, 2018

Study Registration Dates

• First Submitted: April 17, 2008
• First Submitted That Met QC Criteria: April 21, 2008
• First Posted (ESTIMATE): April 22, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): June 17, 2016
• Last Update Submitted That Met QC Criteria: June 16, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: Prostate Cancer; T cells; Gene Transfer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormones
• Other Study ID Numbers: 595-04; W81XWH-05-1-0408