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Protocol Details

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

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 15
Max Age: 70

Referral Letter Required


Population Exclusion(s)

Pregnant Women and Fetuses

Special Instructions

Currently Not Provided


Metastatic Cancer;
Gene Therapy;
Tumor Regression;

Recruitment Keyword(s)



Breast Cancer;
Non-Small Cell Lung Cancer;
Hepatocellular Cancer

Investigational Drug(s)

Anti-ESO murine TCR transduced PBL

Investigational Device(s)



Biological/Vaccine: Anti-NY ESO-1 mTCR PBL
Drug: Cyclophosphamide
Drug: Fludarabine
Drug: Aldesleukin

Supporting Site

National Cancer Institute


The NCI Surgery Branch has developed an experimental therapy for treating patients with cancer that involves taking white blood cells from the patient, growing them in the laboratory in large numbers, genetically modifying them, and then giving the cells back to the patient. In a previous study the NCI Surgery Branch used the anti-ESO-1 gene and a type of virus (retrovirus) to make these tumor fighting cells (anti-ESO-1 cells). About half of the patients who received this treatment experienced shrinking of their tumors. In this study, we are using a slightly different method of producing the anti-ESO-1 cells which we hope will be better in making the tumors shrink.


The purpose of this study is to see if these tumor fighting cells (genetically modified cells) that express the receptor for the ESO-1 molecule on their surface can cause tumors to shrink and to see if this treatment is safe.


- Patients 15 years old and older with cancer that has the ESO-1 molecule on their tumors.


- Work up stage: Patients will be seen as an outpatient at the NIH clinical Center and undergo a history and physical examination, scans, x-rays, lab tests, and other tests as needed

- Leukapheresis: If the patients meet all of the requirements for the study they will undergo leukapheresis to obtain white blood cells to make the anti ESO-1 cells. {Leukapheresis is a common procedure which removes only the white blood cells from the patient.}

- Treatment: Once their cells have grown the patients will be admitted to the hospital for the conditioning chemotherapy, the anti-ESO-1 cells and aldesleukin. They will stay in the hospital for about 4 weeks for the treatment.

- Follow up: Patients will return to the clinic for a physical exam, review of side effects, lab tests, and scans about every 1-3 months for the first year, and then every 6 months to 1 year as long as their tumors are shrinking. Follow up visits take up to 2 days.

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- Measurable (per RECIST v1.0 criteria) metastatic cancer or locally advanced refractory/recurrent malignancy including melanoma that expresses ESO as assessed by one of the following methods: RT-PCR on tumor tissue, immunohistochemistry of resected tissue, or serum antibody reactive with ESO.

- Confirmation of diagnosis of metastatic cancer including melanoma by the NCI Laboratory of Pathology.

- Patients must have previously received first-line standard therapy (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.

- Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible.Patients with surgically resected brain metastases are eligible.

- 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).

Note: Patients may have undergone minor surgical procedures within the past three weeks, as long as all toxicities have recovered to grade 1 or less.

Note: Patients who have previously received ipilimumab and have documented GI toxicity must have a normal colonoscopy with normal colonic biopsies.


- Histologically proven recurrent meningioma or aggressive meningioma.

Note: Confirmation of ESO expression and pathology is not required in patients with definitive radiologic evidence of meningioma who are unresectable, and in whom radiation therapy without biopsy is the standard treatment.

-Recurrent disease/progression after receiving all standard treatments, which must include the following:

-- Surgical resection, if possible.

-- Definitive radiation therapy for unresectable meningioma, or for recurrent meningioma after resection.

- At least 4 weeks post-surgery, and must be at least 3 months post-radiation therapy, with resolution of related toxicities.

- Measurable disease on MRI scan.

- No history of intracranial hemorrhage.

-Patients with a history of neurofibromatosis (NF) may have other stable CNS tumors, such as schwannoma, acoustic neuroma, or ependymoma only if those lesions have been stable for the past 6 months.

-Patients must be on stable dose of steroids for at least 5 days prior to baseline imaging.


- Age greater than or equal to 15 years and less than or equal to 70 years..

- Patient, or their parent(s)/legal guardian(s) (if the patient is < 18 years of age), is able to understand and willing to sign a written informed consent. Written assent will be obtained for participants under the age of 18 as appropriate.

- All participants greater than or equal to 18 years of age must be willing to sign a durable power of attorney.

- Clinical performance status of ECOG 0 or 1.

- Patients aged 15-17 years weigh greater than or equal to 50 kg.

- HLA-A*0201 positive.

- Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for four months after treatment.

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

- Serology

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

-- Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by RT-PCR and be HCV RNA negative.

- Hematology

-- ANC greater than 1000/mm(3) without the support of filgrastim

-- WBC greater than or equal to 3000/mm(3)

-- Platelet count greater than or equal to 100,000/mm(3)

-- Hemoglobin greater than 8.0 g/dl. Subjects may be transfused to reach this cut-off.

- Chemistry:

-- Serum ALT/AST less than 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.

- Subjects must be co-enrolled in protocol 03-C-0277.


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

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

- Active systemic infections requiring anti-infective treatment, coagulation disorders, or any other active or uncompensated major medical illnesses.

- Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immunecompetence 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 cyclophosphamide, fludarabine, or aldesleukin.

- History of coronary revascularization or ischemic symptoms.

- Documented LVEF less than or equal to 45% tested in patients:

-- Age greater than or equal to 65 years

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

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

-- A prolonged history of cigarette smoking (greater than or equal to 20 pack-year smoking history, with cessation within the past two years).

-- Symptoms of respiratory dysfunction.

- Patients who are receiving any other investigational agents.

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Rosenberg SA, Yang JC, Sherry RM, Kammula US, Hughes MS, Phan GQ, Citrin DE, Restifo NP, Robbins PF, Wunderlich JR, Morton KE, Laurencot CM, Steinberg SM, White DE, Dudley ME. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin Cancer Res. 2011 Jul 1;17(13):4550-7. doi: 10.1158/1078-0432.CCR-11-0116. Epub 2011 Apr 15.

Dudley ME, Yang JC, Sherry R, Hughes MS, Royal R, Kammula U, Robbins PF, Huang J, Citrin DE, Leitman SF, Wunderlich J, Restifo NP, Thomasian A, Downey SG, Smith FO, Klapper J, Morton K, Laurencot C, White DE, Rosenberg SA. Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens. J Clin Oncol. 2008 Nov 10;26(32):5233-9. doi: 10.1200/JCO.2008.16.5449. Epub 2008 Sep 22.

Robbins PF, Morgan RA, Feldman SA, Yang JC, Sherry RM, Dudley ME, Wunderlich JR, Nahvi AV, Helman LJ, Mackall CL, Kammula US, Hughes MS, Restifo NP, Raffeld M, Lee CC, Levy CL, Li YF, El-Gamil M, Schwarz SL, Laurencot C, Rosenberg SA. Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J Clin Oncol. 2011 Mar 1;29(7):917-24. doi: 10.1200/JCO.2010.32.2537. Epub 2011 Jan 31.

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Principal Investigator

Referral Contact

For more information:

Steven A. Rosenberg, M.D.
National Cancer Institute (NCI)

Margaret Shovlin, R.N.
National Cancer Institute (NCI)
National Institutes of Health
Building 10
Room 4N115
10 Center Drive
Bethesda, Maryland 20892
(866) 820-4505

Recruitment Center - SB
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Building 10, Room 2-1730, Bethesda, Maryland 20892, United States
(866) 820-4505

Clinical Trials Number:


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