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

• Sponsor: Fred Hutchinson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT02319824
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 2
• Location: 1
• Arm: 1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Sarcoma	Biological: Autologous NY-ESO-1-specific CD8-positive T Lymphocytes; Other: Laboratory Biomarker Analysis; Radiation: Palliative Radiation Therapy	Phase 1

Detailed Description

PRIMARY OBJECTIVES:

1. 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:

1. To look for preliminary evidence of systemic efficacy of NY-ESO-1-specific T-cell therapy following radiation on non-radiated tumors.

2. 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 Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Trial of NY-ESO-1-Specific T Cells in Patients With Metastatic NY-ESO-1-Expressing Sarcomas Receiving Palliative Radiation
• Study Start Date: Jan 1, 2015
• Actual Primary Completion Date: Jun 1, 2015

Arms and Interventions

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.	Biological: Autologous NY-ESO-1-specific CD8-positive T Lymphocytes; Given IV; Other: Laboratory Biomarker Analysis; Correlative studies; Radiation: Palliative Radiation Therapy; Undergo palliative radiation therapy

Outcome Measures

Primary Outcome Measures

1. 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

1. 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)

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington	United States	98109

Sponsors and Collaborators

• Fred Hutchinson Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Seth Pollack, Fred Hutch/University of Washington Cancer Consortium

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Seth Pollack, Responsible Party, Fred Hutchinson Cancer Center
• ClinicalTrials.gov Identifier: NCT02319824
• Other Study ID Numbers: 2721.00; NCI-2014-02154; 2721; 2721.00; K23CA175167; P30CA015704
• First Posted: Dec 18, 2014
• Last Update Posted: Jul 5, 2017
• Last Verified: Apr 1, 2017

• Additional relevant MeSH terms: Sarcoma

Study Results

Participant Flow

Arm/Group Title	Treatment (Radiation and NY-ESO-1-specific T Cells)
Arm/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 2-3 days after completion of radiation therapy.
Period Title: Overall Study
STARTED	2
COMPLETED	2
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Radiation and NY-ESO-1-specific T Cells)
Arm/Group Description	Patients undergo palliative radiation therapy at the discretion of the treating radiation oncologist. Patients then receive NY-ESO-1-specific T cells 2-3 days after completion of radiation therapy. Autologous NY-ESO-1-specific CD8-positive T Lymphocytes
Overall Participants	2
Age, Customized (years) [Mean (Full Range) ]
Mean (Full Range) [years]	40
Sex: Female, Male (Count of Participants)
Female	1 50%
Male	1 50%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	2 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	2 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

treated patients

Arm/Group Title	Treatment (Radiation and NY-ESO-1-specific T Cells)
Arm/Group Description	Patients undergo palliative radiation therapy at the discretion of the treating radiation oncologist. Patients then receive NY-ESO-1-specific T cells I60 minutes 2-3 days after completion of radiation therapy.
Measure Participants	2
Grade 1 Rash (likely related)	1 50%
Grade 2 Shortness of breath (possibly related)	1 50%
Grade 2 Cough (possibly related)	1 50%
Grade 1 Cough (probably related)	1 50%

2. Secondary Outcome

Title	T Cell Transfer Based on Response Evaluation Criteria In Solid Tumors v1.1
Description	RECIST at 6 weeks after treatment (non-radiated tumors only)
Time Frame	At 6 weeks post-treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Radiation and NY-ESO-1-specific T Cells)
Arm/Group Description	Patients undergo palliative radiation therapy at the discretion of the treating radiation oncologist. Patients then receive NY-ESO-1-specific T cells 2-3 days after completion of radiation therapy.
Measure Participants	2
SD	1 50%
PD	1 50%

3. Secondary Outcome

Title	Transferred NY-ESO-1-specific T Cells Based on Flow Cytometry Using Major Histocompatibility Complex Tetramers
Description	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.
Time Frame	Up to 6 weeks post-treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Radiation and NY-ESO-1-specific T Cells)
Arm/Group Description	Patients undergo palliative radiation therapy at the discretion of the treating radiation oncologist. Patients then receive NY-ESO-1-specific T cells 2-3 days after completion of radiation therapy.
Measure Participants	2
Number of patients with <5% of CD8 T cells tet+	2 100%
>5%	0 0%

Adverse Events

Time Frame	6 months
Adverse Event Reporting Description	CTCAE v4.03
Arm/Group Title	Treatment (Radiation and NY-ESO-1-specific T Cells)
Arm/Group Description	Patients undergo palliative radiation therapy at the discretion of the treating radiation oncologist. Patients then receive NY-ESO-1-specific T cells 2-3 days after completion of radiation therapy.
All Cause Mortality
	Treatment (Radiation and NY-ESO-1-specific T Cells)
	Affected / at Risk (%)	# Events
Total	0/2 (0%)
Serious Adverse Events
	Treatment (Radiation and NY-ESO-1-specific T Cells)
	Affected / at Risk (%)	# Events
Total	0/2 (0%)
Other (Not Including Serious) Adverse Events
	Treatment (Radiation and NY-ESO-1-specific T Cells)
	Affected / at Risk (%)	# Events
Total	1/2 (50%)
Respiratory, thoracic and mediastinal disorders
cough	1/2 (50%)	2
shortness of breath	1/2 (50%)	1
Skin and subcutaneous tissue disorders
Rash	1/2 (50%)	1

Limitations/Caveats

This trial was ended early as persistence was not at the level we had hoped and we had the opportunity to pursue a more promising strategy. The data is limited by having only 2 patients.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.