Protocol Number: 07-C-0003

Title:

Phase II Study of Metastatic Cancer that Overexpresses p53 Using Lymphodepleting Conditioning Followed by Infusion of Anti-p53 TCR-Gene Engineered Lymphocytes

Number:

07-C-0003

Summary:

Background:

-The p53 gene normally suppresses tumor growth, but when it is mutated, or damaged, tumors can grow unchecked.

-In cancers where the p53 gene has mutated, an increased level of p53 (overexpression of p53) can be measured in the tumor.

Objectives:

-To determine whether advanced cancers that overexpress p53 can be treated effectively with lymphocytes (white blood cells) that have been genetically engineered to contain an anti-p53 protein.

Eligibility:

-Patients 18 years of age and older with metastatic cancer (cancer that has spread beyond the original site)

-Patient's tumor overexpresses p53

-Patient's leukocyte antigen type is HLA-A 0201

Design:

Patients undergo the following procedures:

-Leukapheresis (on two occasions). This is a method of collecting large numbers of white blood cells. The cells obtained in the first leukapheresis procedure are grown in the laboratory, and the anti-p53 protein is inserted into the cells using an inactivated (harmless) virus in a process called transduction. Cells collected in the second leukapheresis procedure are used to evaluate the effectiveness of the study treatment.

-Chemotherapy. Patients are given chemotherapy through a vein (intravenously, IV) for 1 week to suppress the immune system so that the patient's immune cells do not interfere with the treatment.

-Treatment with anti-p53 cells. Patients receive an IV infusion of the transduced cells containing anti-p53 protein, followed by infusions of a drug called IL-2, which helps boost the effectiveness of the transduced white cells.

-Patients may undergo a tumor biopsy (removal of a small piece of tumor tissue).

-Patients are evaluated with laboratory tests and imaging tests, such as CT scans 4 to 6 weeks after treatment and then once a month for 3 to 4 months to determine the response to treatment.

-Patients have blood tests at 1, 3, 6 and 12 months and then annually for 5 years. After 5 years, they complete a health questionnaire annually for the next 10 years.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Completed Study; data analyses ongoing

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria: This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Special Instructions:

Currently Not Provided

Keyword(s):

Tumor Regression

In Vivo Cell Survival

Toxicity Profile

Metastatic Melanoma

Metastatic Renal Cell Cancer

Recruitment Keyword(s):

Cancer

Metastatic Cancer

Condition(s):

Anti-p53 TCR-Gene

Investigational Drug(s):

Anti-p53 TCR-Gene

Investigational Device(s):

None

Interventions:

Drug: Anti-p53 TCR-Gene

Supporting Site:

National Cancer Institute

Contact(s):

This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Citation(s):

Kawakami Y, Eliyahu S, Delgado CH, Robbins PF, Rivoltini L, Topalian SL, Miki T, Rosenberg SA. Cloning of the gene coding for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3515-9.

Kawakami Y, Eliyahu S, Sakaguchi K, Robbins PF, Rivoltini L, Yannelli JR, Appella E, Rosenberg SA. Identification of the immunodominant peptides of the MART-1 human melanoma antigen recognized by the majority of HLA-A2-restricted tumor infiltrating lymphocytes. J Exp Med. 1994 Jul 1;180(1):347-52.

Kawakami Y, Eliyahu S, Delgado CH, Robbins PF, Sakaguchi K, Appella E, Yannelli JR, Adema GJ, Miki T, Rosenberg SA. Identification of a human melanoma antigen recognized by tumor-infiltrating lymphocytes associated with in vivo tumor rejection. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6458-62.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department Clinical Research Informatics, CC.

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