DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more



Viral Oncoprotein Targeted Autologous T Cell Therapy for Merkel Cell Carcinoma

Information source: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Recurrent Merkel Cell Carcinoma; Stage IV Merkel Cell Carcinoma

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

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: Fred Hutchinson Cancer Research Center

Official(s) and/or principal investigator(s):
Aude Chapuis, Principal Investigator, Affiliation: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

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.

Clinical Details

Official title: Study to Evaluate Cellular Adoptive Immunotherapy Using Polyclonal Autologous CD8+ Antigen-Specific T Cells for Metastatic Merkel Cell Carcinoma

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

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

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

Secondary outcome:

Disease response by RECIST criteria

Functional capacity of transferred T cells

MCC-specific survival

Persistence of transferred T cells in blood and in tumor

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.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

- 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

Locations and Contacts

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium, Seattle, Washington 98109, United States; Recruiting
Aude Chapuis, Phone: 206-667-4369, Email: achapuis@fhcrc.org
Aude Chapuis, Principal Investigator
Additional Information

Starting date: February 2013
Last updated: July 16, 2015

Page last updated: August 23, 2015

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017