Phase 1/2 Study of Metastatic Renal Cancer Using T-Cells Transduced With a T-Cell Receptor Which Recognizes TRAIL Bound to the DR4 Receptor

Summary

Background:

* An experimental cancer treatment procedure involves taking a patient s own tumor or blood cells, modifying them with a gene that targets proteins on the surface of tumor cells, and growing those cells in a laboratory. The modified cells are then given back to the patient by intravenous (IV) transfusion, in the hope that the new cells will attack and destroy the cancer cells without harming healthy tissue.
* This procedure has been used for melanoma patients, and researchers are now attempting to use this treatment for patients with renal (kidney) cancer. In the laboratory, this attack kills nearly all kidney cancers tested, but not normal tissues. However, the effectiveness and possible side effects of this treatment are still being studied.

Objectives:

* To find out if cells modified to target DR4 and TRAIL (two proteins found on the surface of many kidney tumors) are effective in treating kidney cancer.
* To determine the maximum tolerated dose (the highest dose that does not cause unacceptable side effects) of the modified cells.

Eligibility:

* Patients 18 years of age and older with metastatic renal cancer whose disease has not responded to standard treatment.
* Patients will be divided into two study branches: Arm A for those who will be receiving modified cells from their biopsied tumor, and Arm B for those who will be receiving their own modified white blood cells.

Design:

* Five-stage treatment process, outpatient for stages 1 and 5 and inpatient for stages 2 through 4:
* Work-up (1 to 2 weeks): Physical examination, heart and lung function tests, imaging tests, blood and/or tumor samples taken.
* IV chemotherapy (1 week): Cyclophosphamide and fludarabine to prepare for the new cell infusion.
* IV cell infusion and treatment with IL-2 to support the modified cells (4 days).
* Recovery (1 to 2 weeks): Recover from effects of chemotherapy and infusion.
* Follow-up (every 1 to 6 months): Return to clinic for physical exam, review of side effects, other tests.
* Follow-up evaluations will continue to determine the success of the treatment.
* Evaluations during the treatment period:
* Physical examination, including vital signs and body weight checks, and pregnancy test for women who can become pregnant.
* Blood and urine tests.
* Disease evaluation and monitoring on both inpatient and outpatient basis.
* Because researchers do not know the long-term side effects of gene therapy, patients will be asked to participate in long-term follow up for up to 15 years. The follow-up will involve yearly physical exams and medical history, and blood collection (3, 6 and 12 months after treatment, and every year after that).

Conditions

• Renal Cancer
• Kidney Cancer

Interventions

GENETIC

2G-1 TCR Retroviral Vector-Transduced lyn

DRUG

Aldesleukin

DRUG

Cyclophosphamide

DRUG

Fludarabine

DRUG

(PG13-A(F/K-F-SGSG-T2a-B (opt) (2G-1 TCR) retroviral vector-transduced lymphocyte

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• James C Yang, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

99 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2009-03-02

Primary Completion

2012-08-24

Completion

2012-08-24

Countries

• United States

Study Locations