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

• ClinicalTrials.gov Identifier: NCT02319824
• Recruitment Status: Completed
• First Posted: December 18, 2014
• Results First Posted: July 5, 2017
• Last Update Posted: July 5, 2017
• Sponsor: Fred Hutchinson Cancer Center
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Seth Pollack, Fred Hutchinson Cancer Center

Tracking Information

• First Submitted Date: November 5, 2014
• First Posted Date: December 18, 2014
• Results First Submitted Date: April 18, 2017
• Results First Posted Date: July 5, 2017
• Last Update Posted Date: July 5, 2017
• Study Start Date: January 2015
• Actual Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 18, 2017)

Incidence of Adverse Events Measured by the National Cancer Institute Common Terminology Criteria for Adverse Events Version (v)4.03 [ Time Frame: Up to 12 weeks post-treatment ]

CTCAE v4.03

Original Primary Outcome Measures (submitted: December 15, 2014)

Incidence of adverse events measured by the National Cancer Institute Common Terminology Criteria for Adverse Events version (v)4.03 [ Time Frame: Up to 12 weeks post-treatment ]

The highest toxicity grades per patient will be tabulated for adverse events and laboratory measurements, and the number and percent of patients reporting adverse events (all, severe or worse, serious, and related) will be quantified.

Current Secondary Outcome Measures (submitted: April 18, 2017)

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

Original Secondary Outcome Measures (submitted: December 15, 2014)

• T cell transfer based on Response Evaluation Criteria In Solid Tumors v1.1 [ Time Frame: At 6 weeks post-treatment ]
• Transferred genetically engineered NY-ESO-1-specific T lymphocytes based on flow cytometry using major histocompatibility complex tetramers [ Time Frame: Up to 6 weeks post-treatment ]
  This is a composite outcome measure. Summary statistics will be used to for describing changes across time. In addition, the time course of biomarker outcomes will be investigated graphically, by summary plots or individual patient plots. Categorical data analyses and logistic regression will be used to evaluate the associations between correlative measures and clinical outcomes (e.g., response, clinical benefit, time to progression, progression-free survival, and survival). If there is suggestion of meaningful trend, methods such as linear mixed models may be used to characterize the pattern of change over time.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: NY-ESO-1-Specific T-cells in Treating Patients With Advanced NY-ESO-1-Expressing Sarcomas Receiving Palliative Radiation Therapy
• Official Title: A Pilot Trial of NY-ESO-1-Specific T Cells in Patients With Metastatic NY-ESO-1-Expressing Sarcomas Receiving Palliative Radiation
• 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.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Sarcoma

Intervention

• 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

Study Arms

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.

Interventions:

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 9, 2016): 2
• Original Estimated Enrollment (submitted: December 15, 2014): 12
• Study Completion Date: Not Provided
• Actual Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02319824
• Other Study ID Numbers: 2721.00; NCI-2014-02154 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); 2721; 2721.00 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium ); K23CA175167 ( U.S. NIH Grant/Contract ); P30CA015704 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Seth Pollack, Fred Hutchinson Cancer Center
• Original Responsible Party: Fred Hutchinson Cancer Center
• Current Study Sponsor: Fred Hutchinson Cancer Center
• Original Study Sponsor: Same as current
• Collaborators: National Cancer Institute (NCI)

Investigators

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

• PRS Account: Fred Hutchinson Cancer Center
• Verification Date: April 2017