Protocol Number: 08-C-0121

Title:

Phase II Study of Metastatic Cancer that Expresses NY-ESO-1 Using Lymphodepleting Conditioning Followed by Infusion of Anti-NY ESO-1 TCR-Gene Engineered Lymphocytes

Number:

08-C-0121

Summary:

Background:

-This study uses an experimental cancer treatment that uses the patient's own lymphocytes (type of white blood cell), which are specially selected and genetically modified to target and destroy their tumor.

Objectives:

-To test the safety of the treatment and determine if it can cause the patient's tumor to shrink.

Eligibility:

-Patients 18 years of age and older whose cancer has spread beyond the original site and does not respond to standard treatment.

-Patients have tissue type HLA-A*0201.

-Patients' cancer cells have the ESO-1 gene.

Design:

-Workup: Patients have scans, x-rays, laboratory tests, and other tests as needed.

-Patients have leukapheresis to collect cells for laboratory treatment and later reinfusion. For this procedure, whole blood is collected thorough a tube in a vein, the desired cells are extracted from the blood, and the rest of the blood is returned to the patient.

-Chemotherapy: Patients have low-dose chemotherapy for 1 week to prepare the immune system to receive the treated lymphocytes.

-Cell infusion and aldesleukin (IL-2) treatment: Patients receive the lymphocytes by a 30-minute infusion through a vein. Starting within 24 hours of the infusion, they receive high-dose aldesleukin infusions every 8 hours for up to 5 days (maximum15 doses).

-Recovery: Patients rest for 1 to 2 weeks to recover from the effects of chemotherapy and aldesleukin.

-Tumor biopsy: Patients may be asked to undergo a biopsy (surgical removal of a small piece of tumor) after treatment to look at the effects of treatment on the immune cells in the tumor.

-Follow-up: After treatment is completed, patients return to the clinic once a month for several months for physical examinations, a review of side effects, laboratory tests and scans. They may undergo leukapheresis at some visits to look at the effect of treatment on the immune system and check the viability of the infused cells. Patients then return to the NIH clinic once a year for 5 years and then complete a follow-up questionnaire for another 10 years.

-Retreatment: Patients whose tumor shrinks or disappears following treatment and then recurs may receive one additional treatment, using the same regimen of chemotherapy, lymphocyte infusion and IL-2 treatment.

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:

- Metastatic cancer that expresses ESO as assessed by one of the following methods: RT-PCR on tumor tissue, or by immunohistochemistry of resected tissue, or serum antibody reactive with ESO. Metastatic cancer diagnosis will be confirmed by the Laboratory of Pathology at the NCI.

- Patients with melanoma or renal cell cancer must have previously received high dose IL-2 and have been either non-responders (progressive disease) or have recurred. Patients with other histologies, 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.

- Greater than or equal to 18 years of age.

- Willing to sign a durable power of attorney.

- Able to understand and sign the Informed Consent Document.

- Clinical performance status of ECOG 0 or 1.

- Life expectancy of greater than three months.

- Patients of both genders must be willing to practice birth control for four months after receiving the preparative regimen.

- Patients must be HLA-A*0201 positive

- Serology:

-- 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.)

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

-- Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the preparative chemotherapy on the fetus.

- Hematology:

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

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

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

-- Hemoglobin greater than 8.0 g/dl.

- Chemistry:

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

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

-- 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.

- 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).

- Six weeks must have elapsed since prior MDX-010 therapy to allow antibody levels to decline.

- Patients who have previously received MDX-010 or ticilimumab must have a normal colonoscopy with normal colonic biopsies.

EXCLUSION CRITERIA:

- 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.

- 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.

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

- 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).

- Concurrent Systemic steroid therapy

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

- History of coronary revascularization or ischemic symptoms

- Any patient known to have an LVEF less than or equal to 45 percent.

- Documented LVEF of less than or equal to 45 percent tested in patients with:

-- History y 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

-- Age greater than or equal to 60 years old.

- Documented FEV1 less than or equal to 60 percent predicted tested in patients with:

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

-- Symptoms of respiratory dysfunction

Special Instructions:

Currently Not Provided

Keywords:

Metastatic Cancer

Gene Therapy

Immunotherapy

Tumor Regression

Recruitment Keyword(s):

Metastatic Cancer

Metastatic Melanoma

Metastatic Renal Cell Cancer

Condition(s):

Metastatic Melanoma

Metastatic Renal Cell Cancer

Metastatic Cancer

Investigational Drug(s):

(PG13-A2aB-1G4A-LY-3H10 transduced PBL (anti-NY ESO1 TCR PBL))

Investigational Device(s):

None

Intervention(s):

Drug: (PG13-A2aB-1G4A-LY-3H10 transduced PBL (anti-NY ESO1 TCR PBL))

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 J, Nishimura MI, Yu D, Yang JC, Topalian SL, Schwartzentruber DJ, Hwu P, Marincola FM, Sherry R, Leitman SF, Rosenberg SA. Adoptive transfer of cloned melanoma-reactive T lymphocytes for the treatment of patients with metastatic melanoma. J Immunother. 2001 Jul-Aug;24(4):363-73.

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.

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