NY-ESO-1-Specific T-cells in Treating Patients With Advanced NY-ESO-1-Expressing Sarcomas Receiving Palliative Radiation Therapy

Study Overview
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Brief Summary
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This pilot, phase I trial studies the safety of cancer-testis antigen (NY-ESO-1)-specific T cells (a type of immune cell) in treating patients with NY-ESO-1-expressing sarcomas that have spread to other places in the body and are receiving palliative (relief of symptoms and suffering caused by cancer) radiation therapy. Placing a modified gene for NY-ESO-1 into white blood cells may help the body build an immune response to kill tumor cells that express NY-ESO-1. Palliative radiation therapy may help patients with advanced sarcoma live more comfortably. Giving NY-ESO-1-specific T cells following palliative radiation therapy may be a better treatment for patients with sarcomas.

Detailed Description
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PRIMARY OBJECTIVES: I. To evaluate the safety and toxicity of NY-ESO-1-specific T cells when given following high-dose, hypo-fractionated palliative radiation to patients with advanced NY-ESO-1 expressing sarcomas. SECONDARY OBJECTIVES: I. To look for preliminary evidence of systemic efficacy of NY-ESO-1-specific T-cell therapy following radiation on non-radiated tumors. II. To determine whether radiation increases trafficking of adoptively transferred NY-ESO-1-specific T cells by comparing tumor biopsy specimens from radiated and non-radiated tumors. OUTLINE: Patients undergo palliative radiation therapy at the discretion of the treating radiation oncologist. Patients then receive NY-ESO-1-specific T cells intravenously (IV) over 60 minutes 2-3 days after completion of radiation therapy. After completion of study treatment, patients are followed up weekly for 2 weeks, at 4-6, 8, 10, and 12 weeks, and then for up to 6 months.

Official Title
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A Pilot Trial of NY-ESO-1-Specific T Cells in Patients With Metastatic NY-ESO-1-Expressing Sarcomas Receiving Palliative Radiation

Conditions
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Sarcoma

Intervention / Treatment
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* Biological: Autologous NY-ESO-1-specific CD8-positive T Lymphocytes
* Other: Laboratory Biomarker Analysis
* Radiation: Palliative Radiation Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: INCLUSION CRITERIA FOR SCREENING: Histopathological documentation of sarcoma Patients must express NY-ESO-1 in their tumor by immunohistochemistry (IHC) (> 5%) prior to leukapheresis For leukapheresis, patients must meet the following criteria (any exceptions to this will require prior approval by the apheresis director and principal investigator [PI]): Pulse > 45 or < 120 Weight >= 45 kg Temperature =< 38° Celsius (C) (=< 100.4° Fahrenheit [F]) White blood cell count (WBC) >= 2,000 Hematocrit (HCT) >= 30% Platelets >= 75,000 INCLUSION CRITERIA FOR TREATMENT: A diagnosis of a metastatic or unresectable sarcoma Patient must have a biopsy-accessible tumor to be radiated Patient must have consulted with a radiation oncologist who is planning radiation; their radiation oncologist should have documented plans to administer a dose of at least 30 Gy in 5 or fewer fractions Human leukocyte antigen (HLA) type A0201 or A2402 Zubrod (Eastern Cooperative Oncology Group [ECOG]) performance status of '0-2' All patients must have an electrocardiogram (ECG) within 2 weeks of starting conditioning All patients must have an echo or multigated acquisition (MUGA) scan showing ejection fraction (EF) > 50% and normal troponin and creatine kinase MB (CK MB) performed within 90 days of starting treatment Exclusion Criteria: EXCLUSION CRITERIA FOR SCREENING: Patients who do not meet the above inclusion criteria will not receive leukapheresis EXCLUSION CRITERIA FOR TREATMENT: Patients with a history of proven myocarditis, pericarditis, or endocarditis Pregnant women, nursing women, men and women of reproductive ability who are unwilling to use effective contraception or abstinence; women of childbearing potential must have a negative pregnancy test within two weeks prior to study entry Inadequate renal function as indicated by serum creatinine >= 1.5 times the upper limit of normal Inadequate liver function as indicated by total bilirubin >= 1.5 times the upper limit of normal Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >= 2.5 times the upper limit of normal Active symptomatic congestive heart failure Clinically significant hypotension Newly diagnosed cardiac arrhythmia; patients with an arrhythmia that has been stable for at least 3 months will be allowed to participate Known untreated central nervous system (CNS) metastasis Patients with systemic infections requiring antibiotics or chronic maintenance/suppressive therapy Patients receiving systemic anticancer therapy (chemotherapy, biologics, immunotherapy) less than 2 weeks prior to starting radiation Clinically significant autoimmune disorders requiring on-going systemic immune-suppression for control Patients with acquired immunodeficiency syndrome (AIDS) or who are known to be human immunodeficiency virus (HIV) positive are not eligible for this study; testing may have been done up to 3 months prior to treatment Current treatment with steroids Known infection with hepatitis B virus (HBV) and hepatitis C virus (HCV); testing may have been done up to 3 months prior to treatment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (radiation and NY-ESO-1-specific T cells)<br>Patients undergo palliative radiation therapy at the discretion of the treating radiation oncologist. Patients then receive NY-ESO-1-specific T cells IV over 60 minutes 2-3 days after completion of radiation therapy. | Biological: Autologous NY-ESO-1-specific CD8-positive T Lymphocytes<br>* Given IV<br>Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Radiation: Palliative Radiation Therapy<br>* Undergo palliative radiation therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events Measured by the National Cancer Institute Common Terminology Criteria for Adverse Events Version (v)4.03 | CTCAE v4.03 | Up to 12 weeks post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| T Cell Transfer Based on Response Evaluation Criteria In Solid Tumors v1.1 | RECIST at 6 weeks after treatment (non-radiated tumors only) | At 6 weeks post-treatment | 
| Transferred NY-ESO-1-specific T Cells Based on Flow Cytometry Using Major Histocompatibility Complex Tetramers | Over 5% tet+ cells at 6 weeks? Patients may have detectable NY-ESO-1 specific T cells by MHC tetramers but if they are less than 5% this will be considered negative. | Up to 6 weeks post-treatment |