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

Fred Hutchinson Cancer Center (FHCC)

Status and phase: Completed; Phase 1

Conditions: Sarcoma

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

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02319824

NCI-2014-02154 (Registry Identifier)

2721

P30CA015704 (U.S. NIH Grant/Contract)

K23CA175167 (U.S. NIH Grant/Contract)

2721.00 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 2 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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2 participants in 1 patient group

Treatment (radiation and NY-ESO-1-specific T cells)

Experimental group

Description:

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: Palliative Radiation Therapy

Other: Laboratory Biomarker Analysis

Biological: Autologous NY-ESO-1-specific CD8-positive T Lymphocytes