Viral Oncoprotein Targeted Autologous T Cell Therapy for Merkel Cell Carcinoma

NCT01758458 | Terminated Phase 1 DMC

• 4 other identifiers: 2586.00NCI-2012-027792586P30CA015704
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Recurrent Merkel Cell Carcinoma; Stage IV Merkel Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• 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%.

  Up to 4 weeks

• Evidence of response based on "median time to new metastasis"

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

  Up to 4 years

Secondary Outcomes (4)

• Disease response by RECIST criteria

  Up to 4 years

• Functional capacity of transferred T cells

  Up to 4 years

• MCC-specific survival

  Up to 4 years

• Persistence of transferred T cells in blood and in tumor

  Up to 4 years

Study Arms (1)

Treatment (autologous T cells and aldesleukin)

EXPERIMENTAL

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.

Biological: Aldesleukin; Other: Laboratory Biomarker Analysis; Biological: MCPyV TAg-specific Polyclonal Autologous CD8-positive T Cells; Radiation: Radiation Therapy; Biological: Recombinant Interferon Beta

Interventions

Aldesleukin BIOLOGICAL

Given SC

Also known as: 125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2, Recombinant Human Interleukin-2

Treatment (autologous T cells and aldesleukin)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (autologous T cells and aldesleukin)

MCPyV TAg-specific Polyclonal Autologous CD8-positive T Cells BIOLOGICAL

Given IV

Treatment (autologous T cells and aldesleukin)

Radiation Therapy RADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, Irradiate, Irradiated, Irradiation, RADIATION, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Treatment (autologous T cells and aldesleukin)

Recombinant Interferon Beta BIOLOGICAL

Given intralesionally

Also known as: Beta Interferon, Betantrone, Feron, Human Interferon Beta, Interferon Beta, Interferon, Beta, Interferon-B, Interferon-beta, Naferon

Treatment (autologous T cells and aldesleukin)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Carcinoma, Merkel Cell

Interventions

aldesleukin; Radiotherapy; Radiation; Interferon-beta

Condition Hierarchy (Ancestors)

Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Therapeutics; Physical Phenomena; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Aude Chapuis

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 27, 2012
• First Posted: January 1, 2013
• Study Start: February 1, 2013
• Primary Completion: May 1, 2016
• Study Completion: May 1, 2016
• Last Updated: April 19, 2017

Record last verified: 2017-04

Locations

US (1)