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Recurrent Merkel Cell CarcinomaPhase 1/2NCT01758458

Viral Oncoprotein Targeted Autologous T Cell Therapy for Merkel Cell Carcinoma

A Phase 1/2 study testing Aldesleukin, Laboratory Biomarker Analysis and MCPyV TAg-specific Polyclonal Autologous CD8-positive T Cells in people with Recurrent Merkel Cell Carcinoma and Stage IV Merkel Cell Carcinoma, run by Fred Hutchinson Cancer Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Aldesleukin, Laboratory Biomarker Analysis and MCPyV TAg-specific Polyclonal Autologous CD8-positive T Cells
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4 participants
Where
1 siteUnited States
Study dates
Feb 2013to May 2016
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 18Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
Aldesleukin, Laboratory Biomarker Analysis, MCPyV TAg-specific Polyclonal Autologous CD8-positive T Cells, Radiation Therapy, Recombinant Interferon Beta
Medical subject headings
Carcinoma, Merkel Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AldesleukinBiological

    Also called 125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2

    Given SC

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • MCPyV TAg-specific Polyclonal Autologous CD8-positive T CellsBiological

    Given IV

  • Radiation TherapyRadiation

    Also called Cancer Radiotherapy, Irradiate, Irradiated, Irradiation

    Undergo radiation therapy

  • Recombinant Interferon BetaBiological

    Also called Beta Interferon, Betantrone, Feron, Human Interferon Beta

    Given intralesionally

Study groups in NCT01758458
Study groupRoleWhat they receive
Treatment (autologous T cells and aldesleukin)ExperimentalPatients 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.
Receives: Biological: Aldesleukin; Other: Laboratory Biomarker Analysis; Biological: MCPyV TAg-specific Polyclonal Autologous CD8-positive T Cells; Radiation: Radiation Therapy; Biological: Recombinant Interferon Beta

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    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%.

    Measured: Up to 4 weeks

  2. Evidence of response based on "median time to new metastasis"

    Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

    Measured: Up to 4 years

Secondary outcomes (4)

  1. Disease response by RECIST criteria

    Measured: Up to 4 years

  2. Functional capacity of transferred T cells

    Measured: Up to 4 years

  3. MCC-specific survival

    Measured: Up to 4 years

  4. Persistence of transferred T cells in blood and in tumor

    Measured: Up to 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Jan 2013 (estimated)
  2. Study startFeb 2013
  3. Primary completionMay 2016
  4. Study completionMay 2016

Why it stopped: A Phase I/II study (NCT01758458) is now recruiting

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01758458
Sponsor's protocol ID
2586.00
Other IDs
NCI-2012-02779, 2586, 2586.00, P30CA015704
Status last verified
Apr 2017
First submitted
27 Dec 2012
Last updated
19 Apr 2017
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Aldesleukin, Laboratory Biomarker Analysis and MCPyV TAg-specific Polyclonal Autologous CD8-positive T Cells in people with Recurrent Merkel Cell Carcinoma and Stage IV Merkel Cell Carcinoma, run by Fred Hutchinson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 19 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: A Phase I/II study (NCT01758458) is now recruiting). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01758458.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2017.

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