- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01758458
Viral Oncoprotein Targeted Autologous T Cell Therapy for Merkel Cell Carcinoma
Study Overview
Status
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
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Washington
-
Seattle, Washington, United States, 98109
- Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
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
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 |
Intervention / Treatment |
---|---|
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. |
Correlative studies
Undergo radiation therapy
Other Names:
Given SC
Other Names:
Given IV
Given intralesionally
Other Names:
|
What is the study measuring?
Primary Outcome Measures
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
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
Sponsor
Collaborators
Investigators
- Principal Investigator: Aude Chapuis, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Virus Diseases
- Infections
- Neoplasms by Histologic Type
- Neoplasms
- Adenocarcinoma
- Neoplasms, Glandular and Epithelial
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- DNA Virus Infections
- Tumor Virus Infections
- Neuroendocrine Tumors
- Polyomavirus Infections
- Carcinoma, Neuroendocrine
- Carcinoma
- Carcinoma, Merkel Cell
- Physiological Effects of Drugs
- Anti-Infective Agents
- Peripheral Nervous System Agents
- Antiviral Agents
- Anti-HIV Agents
- Anti-Retroviral Agents
- Analgesics
- Sensory System Agents
- Analgesics, Non-Narcotic
- Antineoplastic Agents
- Immunologic Factors
- Interferons
- Aldesleukin
- Interferon-beta
- Interleukin-2
Other Study ID 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.
Clinical Trials on Recurrent Merkel Cell Carcinoma
-
National Cancer Institute (NCI)CompletedRecurrent Merkel Cell Carcinoma | Stage III Merkel Cell Carcinoma AJCC v7 | Stage IV Merkel Cell Carcinoma AJCC v7 | Stage IIIA Merkel Cell Carcinoma AJCC v7 | Stage IIIB Merkel Cell Carcinoma AJCC v7United States
-
National Cancer Institute (NCI)Active, not recruitingAdvanced Merkel Cell Carcinoma | Metastatic Merkel Cell Carcinoma | Pathologic Stage III Cutaneous Merkel Cell Carcinoma AJCC v8 | Clinical Stage III Cutaneous Merkel Cell Carcinoma AJCC v8 | Clinical Stage IV Cutaneous Merkel Cell Carcinoma AJCC v8 | Pathologic Stage IIIA Cutaneous Merkel... and other conditionsUnited States
-
National Cancer Institute (NCI)RecruitingMetastatic Merkel Cell Carcinoma | Refractory Merkel Cell Carcinoma | Locally Advanced Merkel Cell Carcinoma | Unresectable Merkel Cell Carcinoma | Clinical Stage III Cutaneous Merkel Cell Carcinoma AJCC v8 | Clinical Stage IV Cutaneous Merkel Cell Carcinoma AJCC v8United States
-
Melanoma and Skin Cancer Trials LimitedRecruitingNeuroendocrine Tumors | Merkel Cell Carcinoma | Merkel Cell Carcinoma, Stage I | Merkel Cell Carcinoma, Stage II | Merkel Cell Carcinoma, Stage III | Carcinoma Neuroendocrine SkinAustralia, New Zealand
-
University of WashingtonEMD SeronoActive, not recruitingStage III Merkel Cell Carcinoma AJCC v8 | Stage IIIB Merkel Cell Carcinoma AJCC v8 | Stage IIIA Merkel Cell Carcinoma AJCC v8United States
-
National Cancer Institute (NCI)SuspendedPathologic Stage I Cutaneous Merkel Cell Carcinoma AJCC v8 | Pathologic Stage II Cutaneous Merkel Cell Carcinoma AJCC v8 | Pathologic Stage III Cutaneous Merkel Cell Carcinoma AJCC v8United States
-
ImmunityBio, Inc.UnknownStage IIIB Merkel Cell Carcinoma | Stage IV Merkel Cell CarcinomaUnited States
-
University of WashingtonIncyte CorporationRecruitingMerkel Cell Carcinoma | Clinical Stage IV Merkel Cell Carcinoma AJCC v8 | Unresectable Clinical Stage III Merkel Cell Carcinoma AJCC v8United States
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI); EMD SeronoTerminatedStage IV Merkel Cell Carcinoma AJCC v7 | Merkel Cell Polyomavirus InfectionUnited States
-
Claire VerschraegenCompletedMerkel Cell Carcinoma | Pathologic Stage IIIA Merkel Cell Carcinoma AJCC v8 | Pathologic Stage IIIB Merkel Cell Carcinoma AJCC v8United States
Clinical Trials on Laboratory Biomarker Analysis
-
Children's Oncology GroupNational Cancer Institute (NCI)Completed
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Active, not recruitingLeukemia | Acute Lymphoblastic Leukemia | Acute Promyelocytic LeukemiaUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedUntreated Adult Acute Lymphoblastic Leukemia | Untreated Childhood Acute Lymphoblastic LeukemiaUnited States, Canada, Australia, New Zealand, Puerto Rico, Switzerland
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedChildhood Acute Lymphoblastic Leukemia in Remission | Recurrent Childhood Acute Lymphoblastic LeukemiaUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)CompletedLung CancerUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Completed
-
Children's Oncology GroupNational Cancer Institute (NCI)WithdrawnClear Cell Renal Cell Carcinoma | Rhabdoid Tumor of the Kidney | Congenital Mesoblastic Nephroma | Childhood Kidney NeoplasmUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)WithdrawnBreast Carcinoma | BRCA1 Mutation Carrier | BRCA2 Mutation CarrierUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedWilms Tumor and Other Childhood Kidney TumorsUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedChildhood Acute Monoblastic Leukemia (M5a) | Childhood Acute Monocytic Leukemia (M5b) | Childhood Acute Myeloblastic Leukemia Without Maturation (M1) | Childhood Acute Myelomonocytic Leukemia (M4) | Childhood Acute Myeloid Leukemia/Other Myeloid MalignanciesUnited States