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

Phase 1

Completed

Conditions: Sarcoma

Interventions: Biological: Autologous NY-ESO-1-specific CD8-positive T Lymphocytes
Other: Laboratory Biomarker Analysis
Radiation: Palliative Radiation Therapy

Registration Number: NCT02319824

Lead Sponsor: Fred Hutchinson Cancer Center

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 2

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (radiation and NY-ESO-1-specific T cells)	Palliative Radiation Therapy	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.
Treatment (radiation and NY-ESO-1-specific T cells)	Autologous NY-ESO-1-specific CD8-positive T Lymphocytes	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.
Treatment (radiation and NY-ESO-1-specific T cells)	Laboratory Biomarker Analysis	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Transferred NY-ESO-1-specific T Cells Based on Flow Cytometry Using Major Histocompatibility Complex Tetramers	Up to 6 weeks post-treatment	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.
T Cell Transfer Based on Response Evaluation Criteria In Solid Tumors v1.1	At 6 weeks post-treatment	RECIST at 6 weeks after treatment (non-radiated tumors only)