Viral Oncoprotein Targeted Autologous T Cell Therapy for Merkel Cell Carcinoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Fred Hutchinson Cancer Research Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT01758458
First received: December 27, 2012
Last updated: June 23, 2014
Last verified: June 2014
  Purpose

This phase I/II trial studies the side effects and best way to give laboratory treated autologous T cells together with aldesleukin and to see how well it works in treating patients with metastatic merkel cell carcinoma. Biological therapies, such as cellular adoptive immunotherapy, may stimulate the immune system in different ways and stop tumor cells from growing. Aldesleukin may stimulate the white blood cells to kill tumor cells. Giving cellular adoptive immunotherapy with aldesleukin may be a more effective treatment for metastatic merkel cell carcinoma.


Condition Intervention Phase
Recurrent Neuroendocrine Carcinoma of the Skin
Stage IV Neuroendocrine Carcinoma of the Skin
Radiation: radiation therapy
Biological: recombinant interferon beta
Biological: MCPyV TAg-specific polyclonal autologous CD8-positive T cell vaccine
Biological: aldesleukin
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Study to Evaluate Cellular Adoptive Immunotherapy Using Polyclonal Autologous CD8+ Antigen-Specific T Cells for Metastatic Merkel Cell Carcinoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Evidence and nature of toxicity related to the study treatment assessed using National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: Yes ]
    The treatment will be considered to have an acceptable safety profile if the observed toxicity rate is consistent with a true rate that does not exceed 30%.

  • Evidence of response based on "median time to new metastasis" [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.


Secondary Outcome Measures:
  • Persistence of transferred T cells in blood and in tumor [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
  • Functional capacity of transferred T cells [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
  • Disease response by RECIST criteria [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
  • MCC-specific survival [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 16
Study Start Date: February 2013
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (autologous T cells and aldesleukin)

Patients undergo radiation therapy or recombinant interferon beta intralesional injection within day -3 to day -1.

Patients receive MCPyV TAg-specific polyclonal autologous CD8-positive T cell infusion IV on day 1 and aldesleukin SC every 12 hours on days 1-14. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.

Patients with continued presence of detectable metastatic disease 8 weeks after the first infusion may repeat the treatment regimen including radiation therapy or recombinant interferon beta injection.

Radiation: radiation therapy
Undergo radiation therapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Biological: recombinant interferon beta
Given intralesionally
Other Names:
  • Betantrone
  • Betaseron
  • IFN-B
  • Naferon
  • Rebif
Biological: MCPyV TAg-specific polyclonal autologous CD8-positive T cell vaccine
Given IV
Other Name: MCPyV TAg-specific polyclonal autologous CD8-positive T cells
Biological: aldesleukin
Given SC
Other Names:
  • IL-2
  • Proleukin
  • recombinant human interleukin-2
  • recombinant interleukin-2
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the safety and potential toxicities associated with treating patients with metastatic merkel cell carcinoma (MCC) by combined myosin heavy chain (MHC) up-regulation therapy and adoptive transfer of merkel cell polyomavirus (MCPyV) T-antigen (TAg)-specific polyclonal autologous cluster of differentiation (CD)8+ T cells.

II. Determine the antitumor efficacy associated with treating patients with metastatic MCC by combined MHC up-regulation therapy and adoptive transfer of MCPyV TAg-specific polyclonal autologous CD8+ T cells.

SECONDARY OBJECTIVES:

I. Determine the in vivo persistence and where evaluable, migration to tumor sites of adoptively transferred polyclonal CD8+ T cells targeting the MCPyV TAg.

II. Determine the in vivo functional capacity of adoptively transferred polyclonal CD8+ T cells targeting the MCPyV TAg.

OUTLINE:

Patients undergo radiation therapy or recombinant interferon beta intralesional injection within day -3 to day -1.

Patients receive MCPyV TAg-specific polyclonal autologous CD8-positive T cell vaccine intravenously (IV) on day 1 and aldesleukin subcutaneously (SC) every 12 hours on days 1-14. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.

Patients with continued presence of detectable metastatic disease 8 weeks after the first infusion may repeat the treatment regimen including radiation therapy or recombinant interferon beta injection.

After completion of study treatment, patients are followed up every 3 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histopathological documentation of MCC concurrent with the diagnosis of metastatic disease
  • Evidence of MCPyV TAg tumor expression
  • Available peptide-MHC pair that can be folded into a tetramer for which MCPyV TAg-specific cells can be generated and reactivity to cell lines expressing MCPyV TAg with the corresponding human leukocyte antigen (HLA)
  • Bi-dimensionally measurable disease by palpation, clinical exam, or radiographic imaging (x-ray, computed tomography [CT] scan, positron emission tomography [PET] scan, magnetic resonance imaging [MRI], or ultrasound)
  • At least 3 weeks must have passed since any of the following: systemic corticosteroids, immunotherapy (for example, interleukins, MCC vaccines, intravenous immunoglobulin, expanded polyclonal tumor infiltrating lymphocyte [TIL] or lymphokine-activated killer [LAK] therapy), pentoxifylline, other small molecule or chemotherapy cancer treatment, other investigational agents or other agents that target merkel cell carcinoma

Exclusion Criteria:

  • Unable to generate antigen-specific MCPyV TAg-specific CD8+ T cells for infusions
  • Active infections or oral temperature > 38.2 Celsius (C) fewer than 72 hours prior to receiving study treatment or systemic infection requiring chronic maintenance or suppressive therapy
  • Eastern Cooperative Oncology Group (ECOG) performance status > 2
  • White blood cell (WBC) < 2000/mcl
  • Hemoglobin (Hb) < 8 g/dL
  • Absolute neutrophil count (ANC) < 1000/mcl
  • Platelets < 50,000/mcl
  • New York Heart Association functional class III-IV heart failure, symptomatic pericardial effusion, stable or unstable angina, symptoms of coronary artery disease, congestive heart failure, clinically significant hypotension, or an ejection fraction of =< 30 % (echocardiogram or multi gated acquisition scan [MUGA])
  • Clinically significant pulmonary dysfunction, as determined by medical history and physical exam; patients so identified will undergo pulmonary functions testing and those with forced expiratory volume in one second (FEV1) < 2.0 L or diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin [Hgb]) < 50% will be excluded
  • Creatinine clearance < 30 ml/min which cannot be attributed to MCC metastasis
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 5 x upper limit of normal (ULN)
  • Bilirubin > 3 x ULN which cannot be attributed to MCC metastasis
  • Active autoimmune disease (e.g. systemic lupus erythematosus, vasculitis, infiltrating lung disease, inflammatory bowel disease) whose possible progression during treatment would be considered unacceptable by the investigators
  • Symptomatic and untreated central nervous system (CNS) metastasis; however, patients with 1-2 asymptomatic, less than 1 cm brain/CNS metastases without significant edema may be considered for treatment; if sub-centimeter CNS lesions are noted at study entry, then a repeat imaging will be performed if more than 4 weeks have elapsed from the last scan
  • Any condition or organ toxicity that is deemed by the principal investigator (PI) or the attending physician to place the patient at unacceptable risk for treatment on the protocol
  • Pregnant women, nursing mothers, men or 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 entry
  • Clinically significant and ongoing immune suppression including, but not limited to, systemic immunosuppressive agents such as cyclosporine or corticosteroids, chronic lymphocytic leukemia (CLL), uncontrolled human immunodeficiency virus (HIV) infection, or solid organ transplantation
  • Patients may not be on any other treatments for their cancer aside from those included in the protocol; patients may not undergo another form of treatment concurrently with this study
  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: NCT01758458

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Aude Chapuis    206-667-4369      
Principal Investigator: Aude Chapuis         
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: Aude Chapuis 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: NCT01758458     History of Changes
Other Study ID Numbers: 2586.00, NCI-2012-02779, 2586.00, P30CA015704
Study First Received: December 27, 2012
Last Updated: June 23, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Neuroendocrine
Skin Neoplasms
Carcinoma
Carcinoma, Merkel Cell
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Skin Diseases
Polyomavirus Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Aldesleukin
Interferons
Interleukin-2
Interferon-beta
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents

ClinicalTrials.gov processed this record on September 22, 2014