Protocol Number: 09-C-0047

Title:

Phase I/II Study of Metastatic Cancer that Expresses Carcinoembryonic Antigen (CEA) using Lymphodepleting Conditioning Followed by Infusion of Anti-CEA TCR-Gene Engineered Lymphocytes

Number:

09-C-0047

Summary:

Background:

- CEA is a protein present mostly in cancer cells.

- An experimental procedure developed for treating patients with cancer uses blood cells found in their tumors or bloodstream. These cells are genetically modified using the anti-CEA gene and a type of virus. The modified cells (anti-CEA cells) are grown in the laboratory and then given back to the patient to try to decrease the size of the tumors. This is called gene therapy.

Objectives:

- To determine whether advanced cancers that that express the CEA antigen can be treated effectively with lymphocytes (white blood cells) that have been genetically engineered to contain an anti-CEA protein.

Eligibility:

- Patients 18 years of age and older with metastatic cancer (cancer that has spread beyond the original site) and for whom standard treatments are not effective.

- Patients' tumors express the CEA antigen.

- Patients have the HLA-A*0201 antigen.

Design:

- Workup with scans, x-rays and other tests.

- Leukapheresis to obtain cells for preparing the anti-CEA cells for later infusion.

- 1 week of chemotherapy to prepare the immune system for receiving the anti-CEA cells.

- Infusion of anti-CEA cells, followed by interleukin-2 (IL-2) treatment. The cells are given as an infusion through a vein. IL-2 is given as a 15-minute infusion through a vein every 8 hours for a maximum of 15 doses.

- 1-2 weeks of recovery from the effects of chemotherapy and IL-2.

- Periodic follow-up clinic visits after hospital discharge for physical examination, review of treatment side effects, laboratory tests and scans every 1 to 6 months.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

a. Metastatic cancer that expresses CEA as assessed by one of the following methods:

- Immunohistochemistry of resected tissue, assessed by IHC in the CLIA approved test in the Laboratory of Pathology, CCR, NCI, NIH. Since the affinity of the antibody is weak, a result of greater than or equal to 1+ is considered positive.

- Detection of elevated levels of circulating CEA using a standard clinical ELISA assay. Results will be considered positive if CEA level is greater than 10 mcg/L. Metastatic cancer diagnosis will be confirmed by the Laboratory of Pathology at the NCI.

b. Patients must have previously received systemic standard care (or effective salvage chemotherapy regimens) for metastatic disease, if known to be effective for that disease, and have been either non-responders (progressive disease) or have recurred.

c. Greater than or equal to 18 years of age.

d. Willing to sign a durable power of attorney

e. Able to understand and sign the Informed Consent Document

f. Clinical performance status of ECOG 0 or 1.

g. Life expectancy of greater than three months.

h. Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for up to four months after receiving the preparative regimen.

i. Patients must be HLA-A*0201 positive

j. Serology:

1. Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune-competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.)

2. Seronegative for hepatitis B antigen and hepatitis C antibody unless antigen negative.

k. Hematology:

1. Absolute neutrophil count greater than 1000/mm(3) without the support of filgrastim.

2. WBC (greater than 3000/mm(3)).

3. Platelet count greater than 100,000/mm(3).

4. Hemoglobin greater than 8.0 g/dl.

l. Chemistry:

1. Serum ALT/AST less or equal to 2.5 times the upper limit of normal.

2. Serum creatinine less than or equal to 1.6 mg/dl.

3. Total bilirubin less than or equal to 1.5 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.

m. More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients' toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo).

EXCLUSION CRITERIA:

a. Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.

b. Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.

c. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).

d. Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).

e. Concurrent systemic steroid therapy

f. History of severe immediate hypersensitivity reaction to any of the agents used in this study.

g. History of coronary revascularization or ischemic symptoms

h. Any patient known to have an LVEF less than or equal to 45%.

i. Documented LVEF of less than or equal to 45% tested in patients with:

1. History of ischemic heart disease, chest pain, or clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block

2. Age greater than or equal to 60 years old

j. Documented FEV1 less than or equal to 60% predicted tested in patients with:

1. A prolonged history of cigarette smoking (20 pk/year of smoking within the past 2 years).

2. Symptoms of respiratory dysfunction

Special Instructions:

Currently Not Provided

Keywords:

Metastatic Cancer

Tumor Regression

Safety

Immunotherapy

Recruitment Keyword(s):

None

Condition(s):

Metastatic Cancer

Investigational Drug(s):

(PG13-CEA_TCR (Anti-CEA TCR PBL)

Investigational Device(s):

None

Intervention(s):

Drug: (PG13-CEA_TCR (Anti-CEA TCR PBL)

Drug: Aldesleukin

Supporting Site:

National Cancer Institute

Contact(s):

Recruitment Center - SB
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Building 10, Room 2-1730, Bethesda, Maryland 20892, United States
Phone: (866) 820-4505
Fax: (301) 451-1927
Electronic Address: ncisbirc@mail.nih.gov

Citation(s):

Dudley ME, Wunderlich JR, Robbins PF, Yang JC, Hwu P, Schwartzentruber DJ, Topalian SL, Sherry R, Restifo NP, Hubicki AM, Robinson MR, Raffeld M, Duray P, Seipp CA, Rogers-Freezer L, Morton KE, Mavroukakis SA, White DE, Rosenberg SA. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science. 2002 Oct 25;298(5594):850-4. Epub 2002 Sep 19.

Gattinoni L, Powell DJ Jr, Rosenberg SA, Restifo NP. Adoptive immunotherapy for cancer: building on success. Nat Rev Immunol. 2006 May;6(5):383-93.

Dudley ME, Wunderlich JR, Yang JC, Sherry RM, Topalian SL, Restifo NP, Royal RE, Kammula U, White DE, Mavroukakis SA, Rogers LJ, Gracia GJ, Jones SA, Mangiameli DP, Pelletier MM, Gea-Banacloche J, Robinson MR, Berman DM, Filie AC, Abati A, Rosenberg SA. Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J Clin Oncol. 2005 Apr 1;23(10):2346-57.

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