Viral Oncoprotein Targeted Autologous T Cell Therapy for Merkel Cell Carcinoma

April 17, 2017 updated by: Aude Chapuis, Fred Hutchinson Cancer Center
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 merkel cell carcinoma that has spread from the primary site (place where it started) to other places in the body. 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 better treatment for metastatic merkel cell carcinoma.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 at least 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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
4

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Washington
      • Seattle, Washington, United States, 98109
        • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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
  • Cardiac ejection fraction >= 40% (multigated acquisition [MUGA] or echocardiogram); for patients with significant risk factors for coronary artery disease (CAD) (including family history, hypertension, and/or dyslipidemia), or age > 50, stress echo or stress thallium testing is required

Exclusion Criteria:

  • Unable to generate antigen-specific MCPyV TAg-specific CD8+ T cells for infusions
  • Active infections 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 =< 40 % (echocardiogram or 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 at least 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.
Other: Laboratory Biomarker Analysis
Correlative studies
Radiation: Radiation Therapy
Undergo radiation therapy
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • Irradiation
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation
  • RADIATION
Biological: Aldesleukin
Given SC
Other Names:
  • Proleukin
  • 125-L-Serine-2-133-interleukin 2
  • r-serHuIL-2
  • Recombinant Human IL-2
  • Recombinant Human Interleukin-2
Biological: MCPyV TAg-specific Polyclonal Autologous CD8-positive T Cells
Given IV
Biological: Recombinant Interferon Beta
Given intralesionally
Other Names:
  • Beta Interferon
  • Betantrone
  • Feron
  • Human Interferon Beta
  • Interferon Beta
  • Interferon, Beta
  • Interferon-B
  • Interferon-beta
  • Naferon

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
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%.
Up to 4 weeks
Evidence of response based on "median time to new metastasis"
Time Frame: Up to 4 years
Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
Up to 4 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Disease response by RECIST criteria
Time Frame: Up to 4 years
Up to 4 years
Functional capacity of transferred T cells
Time Frame: Up to 4 years
Up to 4 years
MCC-specific survival
Time Frame: Up to 4 years
Up to 4 years
Persistence of transferred T cells in blood and in tumor
Time Frame: Up to 4 years
Up to 4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fred Hutchinson Cancer Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Cancer Institute (NCI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Aude Chapuis, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 27, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 27, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 1, 2013

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 19, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 17, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2586.00 (Other Identifier: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium)
  • P30CA015704 (U.S. NIH Grant/Contract)
  • 2586
  • NCI-2012-02779 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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