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

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

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.

Study Overview

• Status: Completed
• Conditions: Sarcoma
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Radiation: Palliative Radiation Therapy; Biological: Autologous NY-ESO-1-specific CD8-positive T Lymphocytes

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.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutch/University of Washington Cancer Consortium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment (radiation and NY-ESO-1-specific T cells); 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.	Other: Laboratory Biomarker Analysis; Correlative studies; Radiation: Palliative Radiation Therapy; Undergo palliative radiation therapy; Biological: Autologous NY-ESO-1-specific CD8-positive T Lymphocytes; Given IV

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Fred Hutchinson Cancer Center
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (ACTUAL): June 1, 2015

Study Registration Dates

• First Submitted: November 5, 2014
• First Submitted That Met QC Criteria: December 15, 2014
• First Posted (ESTIMATE): December 18, 2014

Study Record Updates

• Last Update Posted (ACTUAL): July 5, 2017
• Last Update Submitted That Met QC Criteria: April 18, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma
• Other Study ID Numbers: 2721.00 (OTHER: Fred Hutch/University of Washington Cancer Consortium); P30CA015704 (U.S. NIH Grant/Contract); K23CA175167 (NIH); 2721; NCI-2014-02154 (REGISTRY: CTRP (Clinical Trial Reporting Program))