Viral Oncoprotein Targeted Autologous T Cell Therapy for Merkel Cell Carcinoma

Recurrent Merkel Cell Carcinoma Clinical Trial

Official title:

Viral Oncoprotein Targeted Autologous T Cell Therapy for Merkel Cell Carcinoma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01758458
• Other study ID #: 2586.00
• Secondary ID: NCI-2012-0277925
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: December 27, 2012
• Last updated: April 17, 2017
• Start date: February 2013
• Est. completion date: May 2016

Study information

• Verified date: April 2017
• Source: Fred Hutchinson Cancer Research Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: May 2016
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Merkel Cell
• Recurrent Merkel Cell Carcinoma
• Stage IV Merkel Cell Carcinoma

Intervention

Biological:
• Aldesleukin
Given SC

Other:
• Laboratory Biomarker Analysis
Correlative studies

Biological:
• MCPyV TAg-specific Polyclonal Autologous CD8-positive T Cells
Given IV

Radiation:
• Radiation Therapy
Undergo radiation therapy

Biological:
• Recombinant Interferon Beta
Given intralesionally

Locations

Country	Name	City	State
United States	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Research Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Disease response by RECIST criteria		Up to 4 years
Secondary	Functional capacity of transferred T cells		Up to 4 years
Secondary	MCC-specific survival		Up to 4 years
Secondary	Persistence of transferred T cells in blood and in tumor		Up to 4 years