NY-ESO-1 Specific T Cells After Cyclophosphamide in Treating Patients With Advanced Synovial Sarcoma or Myxoid/Round Cell Liposarcoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Fred Hutchinson Cancer Research Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT02059850
First received: February 7, 2014
Last updated: July 28, 2014
Last verified: July 2014
  Purpose

This phase I trial studies the side effects and best way to give NY-ESO-1 specific T cells after cyclophosphamide in treating patients with advanced synovial sarcoma or myxoid/round cell liposarcoma. Placing a gene that has been created in the laboratory into white blood cells may make the body build an immune response to kill tumor cells. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving NY-ESO-1 specific T cells with cyclophosphamide may kill more tumor cells.


Condition Intervention Phase
Adult Liposarcoma
Adult Synovial Sarcoma
Recurrent Adult Soft Tissue Sarcoma
Stage III Adult Soft Tissue Sarcoma
Stage IV Adult Soft Tissue Sarcoma
Drug: cyclophosphamide
Biological: NY-ESO-1-specific T cells
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Study To Determine the Feasibility of Treating Synovial Sarcoma and Myxoid/ Round Cell Liposarcoma Using Autologous NY-ESO-1 Specific CD8+ T Cells With Cyclophosphamide Pre-Conditioning But Without the Use of IL-2

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Incidence of grade III or greater toxicity graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 [ Time Frame: Up to 10 weeks ] [ Designated as safety issue: Yes ]
    The type and grade of toxicities noted during therapy will be summarized for each dose level. All adverse events noted by the investigator will be tabulated according to the affected body system. Descriptive statistics will be used to summarize changes from baseline in clinical laboratory parameters.


Secondary Outcome Measures:
  • Persistence of tetramer positive T cells [ Time Frame: At 4 weeks ] [ Designated as safety issue: No ]
    The standard deviation and variance will be determined.

  • Persistence of tetramer positive T cells [ Time Frame: At 10 weeks ] [ Designated as safety issue: No ]
    The standard deviation and variance will be determined.


Estimated Enrollment: 12
Study Start Date: July 2014
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (cyclophosphamide, NY-ESO-1 specific CD8+ T cells)
Patients receive cyclophosphamide IV on days -3 and -2 and NY-ESO-1 specific CD8+ T cells IV over 60 minutes on day 0.
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Biological: NY-ESO-1-specific T cells
Given IV
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To confirm the safety of cancer-testis antigen (NY-ESO-1) specific T cells in patients with advanced synovial sarcoma and myxoid/round cell liposarcoma following conditioning with high dose cyclophosphamide.

SECONDARY OBJECTIVES:

I. To confirm the persistence of NY-ESO-1 tetramer positive cells in the peripheral blood at 10 weeks after T cell infusion for synovial sarcoma and myxoid/round cell liposarcoma patients receiving NY-ESO-1 specific T cells following cyclophosphamide conditioning but not post-infusion interleukin (IL)-2.

OUTLINE:

Patients receive cyclophosphamide intravenously (IV) on days -3 and -2 and NY-ESO-1 specific cluster of differentiation (CD)8+ T cells IV over 60 minutes on day 0.

After completion of study treatment, patients are followed up for up to 12 weeks.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histopathological documentation of sarcoma
  • FOR LEUKAPHERESIS (SCREENING):
  • Pulse > 45 or < 120
  • Weight >= 45 kg
  • Temperature =< 38 Celsius (C) (=< 100.4 Fahrenheit [F])
  • White blood cell (WBC) >= 2,000
  • Hematocrit (HCT) >= 30%
  • Platelets >= 75,000
  • A diagnosis of synovial sarcoma and myxoid/ round cell liposarcoma
  • Patients must have "advanced disease"; usually, this will mean metastatic disease; this may also be multiply recurrent disease or locally advanced disease; locally advanced disease is defined for this study as disease where a mutilating surgery is required and the patient is more likely than not to die of their disease despite an aggressive operation; patients with metastatic disease that has been resected or radiated are allowed to participate; Response Evaluation Criteria in Solid Tumors (RECIST) evaluable disease is not necessary for participation
  • NY-ESO-1 positive by immunohistochemistry (IHC) (for this study, even a small level of positivity is acceptable); for patients with < 5% NY-ESO-1 by IHC positivity, the level of staining should be discussed with the patient and they should be informed that this will likely effect the efficacy of the therapy; this conversation must be documented in the patient's medical chart
  • Human leukocyte antigen (HLA)-A0201 or HLA-A2402
  • Zubrod performance status of '0-1'
  • All patients must have an electrocardiogram (ECG) within 2 weeks of starting conditioning
  • All patients must have a stress test within 6 months of starting treatment showing no evidence of cardiac ischemia
  • All patients must have an echo or multi gated acquisition scan (MUGA) scan showing ejection fraction (EF) > 50% and normal troponin and creatine kinase (CK) myoglobin binding (MB) (echo may be done at the time of stress test as a stress echo); if the patient has received cardiotoxic chemotherapy such as Adriamycin, they must have had an echo or MUGA scan since completing this treatment
  • If there is a patient with an NY-ESO-1 expressing soft tissue sarcoma who would be otherwise eligible for the trial, which is either not synovial sarcoma (SS) or myxoid/round cell liposarcoma (MRCL) or there is controversy about the diagnosis, eligibility will be decided by the principal investigator (PI)
  • Patients must have NY-ESO-1 specific cells already produced or in production; these cells may be either in the process of their final expansion (for fresh infusion) or expanded and frozen at the time of enrollment

Exclusion Criteria:

  • Patients for whom we are unable to generate NY-ESO-1 specific cells
  • Pregnant women, nursing women, and 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
  • Serum creatinine > 1.6 mg/dL or glomerular filtration rate < 50
  • Serum glutamic oxaloacetic transaminase (SGOT) > 150 IU or > 3x upper limit of normal
  • Bilirubin > 1.6 mg/dL
  • Prothrombin time > 1.5 x control
  • Active symptomatic congestive heart failure
  • Clinically significant hypotension
  • Newly diagnosed cardiac arrhythmia; patients with an arrhythmia that has been stable for at least 6 months will be allowed to participate
  • Untreated central nervous system (CNS) metastasis; patients with CNS metastasis will be allowed on study once treated
  • Patients with systemic infections requiring antibiotics or chronic maintenance/ suppressive therapy; once the infection in question has resolved, patients may participate
  • Systemic anticancer treatments (including chemotherapy and biologics) less than 3 weeks prior to T cell therapy; locally directed therapy (e.g. radiation) 2 weeks prior to cell infusion
  • Clinically significant autoimmune disorders requiring systemic immunosuppression for control
  • Patients who are known to be human immunodeficiency virus (HIV) positive are not eligible for this study
  • Current treatment with steroids
  • Known infection with hepatitis B virus (HBV) and hepatitis C virus (HCV); (if a patient was not tested at the time of their leukapheresis, they must be tested prior to receiving T cell infusion; if testing was done for leukapheresis, this is adequate)
  • Patients with a history of proven myocarditis, pericarditis, and/ or endocarditis
  • Patients who do not meet the screening inclusion criteria will not be leukapheresed
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02059850

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Seth Pollack    206-667-6629      
Principal Investigator: Seth Pollack         
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: Seth Pollack Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT02059850     History of Changes
Other Study ID Numbers: 2720.00, NCI-2013-02464, 2720.00, K23CA175167, P30CA015704
Study First Received: February 7, 2014
Last Updated: July 28, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Liposarcoma
Sarcoma, Synovial
Sarcoma
Neoplasms, Adipose Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Connective Tissue
Cyclophosphamide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on July 31, 2014