Clinical trial NCT00004178: Gene Therapy in Treating Patients With Cancer
Official title: Phase I Study of T Cells Modified With Chimeric AntiCEA Immunoglobulin-T Cell Receptors (IgTCR) in Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Keywords: 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 III prostate 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
Lead sponsor: Roger Williams Medical Center
Sponsor class: OTHER
Collaborators: name: Beth Israel Deaconess Medical Center
First posted: 2004-04-19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
Study officials:
affiliation: Beth Israel Deaconess Medical Center
name: Richard P. Junghans, MD, PhD
role: STUDY_CHAIR
References: