Gene Therapy in Treating Patients With Cancer

Study Overview
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Brief Summary
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RATIONALE: Inserting a gene that has been created in the laboratory into a person's white blood cells may make the body build an immune response to kill cancer cells. PURPOSE: Phase I trial to study the effectiveness of gene therapy in treating patients who have cancer that has not responded to previous therapy.

Detailed Description
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OBJECTIVES: Determine the safety and maximum tolerated dose of T cells activated in vitro and modified with chimeric anti-CEA immunoglobulin T cell receptors (Ig TCR) in patients with CEA expressing adenocarcinoma. Determine the pharmacokinetics of this regimen by the persistence of modified T cells in the blood of these patients. Evaluate the immunogenicity of murine sequences in chimeric anti-CEA Ig TCR. Assess immunologic parameters which correlate with the efficacy of this regimen in these patients. Evaluate, in a preliminary manner, the efficacy of this regimen in patients with CEA bearing tumors. OUTLINE: This is a dose escalation study. Peripheral blood lymphocytes (PBL) are harvested. PBL are activated in vitro and then modified with recombinant chimeric anti-CEA immunoglobulin T cell receptors (Ig TCR). Ig TCR modified T cells are reinfused over 30-60 minutes. The estimated maximum tolerated dose (MTD) is defined as the dose at which 2 of 6 patients experience unacceptable toxicity. If the MTD is not reached within the first cohort, a second cohort of 3 patients then receives 4 doses of modified T cells at a higher dose. Patients are followed every 2 weeks for 2 months. PROJECTED ACCRUAL: A total of 6-9 patients will be accrued for this study.

Official Title
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Phase I Study of T Cells Modified With Chimeric AntiCEA Immunoglobulin-T Cell Receptors (IgTCR) in Adenocarcinoma

Conditions
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Cancer

Intervention / Treatment
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* Biological: therapeutic autologous lymphocytes


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically proven CEA expressing adenocarcinoma Serum CEA levels greater than 10 ng/mL Failed standard therapy Measurable disease PATIENT CHARACTERISTICS: Age: 18 and over Performance status: 0-2 Life expectancy: Greater than 2 months Hematopoietic: Not specified Hepatic: No significant hepatic disease Bilirubin no greater than 3 mg/dL No active clinical disease caused by hepatitis B Renal: No significant renal disease Creatinine no greater than 3 mg/dL Cardiovascular: No significant cardiovascular disease Pulmonary: No significant pulmonary disease Other: Not pregnant Negative pregnancy test Fertile patients must use effective contraception No significant endocrine, rheumatologic, or allergic disease No active clinical disease caused by cytomegalovirus or tuberculosis HIV negative PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: At least 4 weeks since prior chemotherapy Endocrine therapy: Not specified Radiotherapy: At least 4 weeks since prior radiotherapy Surgery: Not specified

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: therapeutic autologous lymphocytes|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage III prostate cancer, stage III colon cancer, stage IV colon cancer, stage III gastric cancer, stage IV gastric cancer, recurrent gastric cancer, recurrent non-small cell lung cancer, stage II pancreatic cancer, stage III pancreatic cancer, recurrent pancreatic cancer, stage III rectal cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer, stage II esophageal cancer, stage III esophageal cancer, stage IV esophageal cancer, recurrent esophageal cancer, stage III cervical cancer, recurrent cervical cancer, stage IVB cervical cancer, stage IVA cervical cancer, adenocarcinoma of the prostate, stage III renal cell cancer, stage IV renal cell cancer, recurrent renal cell cancer, stage III ovarian epithelial cancer, stage IV ovarian epithelial cancer, recurrent ovarian epithelial cancer, adenocarcinoma of the stomach, extensive stage small cell lung cancer, recurrent small cell lung cancer, stage III vaginal cancer, stage IVA vaginal cancer, stage IVB vaginal cancer, recurrent vaginal cancer, localized unresectable adult primary liver cancer, advanced adult primary liver cancer, recurrent adult primary liver cancer, stage III endometrial carcinoma, stage IV endometrial carcinoma, recurrent endometrial carcinoma, small intestine adenocarcinoma, unresectable gallbladder cancer, recurrent gallbladder cancer, unresectable extrahepatic bile duct cancer, recurrent extrahepatic bile duct cancer, recurrent small intestine cancer, stage III bladder cancer, recurrent bladder cancer, stage IV bladder cancer, stage IV prostate cancer, recurrent prostate cancer, stage IV non-small cell lung cancer, stage III salivary gland cancer, stage IV salivary gland cancer, recurrent salivary gland cancer, duct cell adenocarcinoma of the pancreas, ovarian undifferentiated adenocarcinoma, adenocarcinoma of the lung, adenocarcinoma of the esophagus, intestinal adenocarcinoma of the stomach, adenocarcinoma of the colon, diffuse adenocarcinoma of the stomach, mixed adenocarcinoma of the stomach, mucinous adenocarcinoma of the colon, signet ring adenocarcinoma of the colon, adenocarcinoma of the rectum, adenocarcinoma of the gallbladder, mucinous adenocarcinoma of the rectum, signet ring adenocarcinoma of the rectum, adenocarcinoma with squamous metaplasia of the gallbladder, adenocarcinoma of the extrahepatic bile duct, ovarian serous cystadenocarcinoma, ovarian mucinous cystadenocarcinoma, ovarian endometrioid adenocarcinoma, ovarian clear cell cystadenocarcinoma, vaginal adenocarcinoma, vaginal clear cell adenocarcinoma, endometrial adenocarcinoma, cervical adenocarcinoma, adenocarcinoma of the bladder, salivary gland adenocarcinoma, adenocarcinoma of unknown primary, adenocarcinoma of the pancreas, stage IV pancreatic cancer