Clinical Trial: Localized Radiation Therapy or Recombinant Interferon Beta and Avelumab With or Without Cellular Adoptive Immunotherapy in Treating Patients With Metastatic Merkel Cell Carcinoma

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Study to Evaluate Cellular Adoptive Immunotherapy Using Polyclonal Autologous CD8+ Antigen-Specific T Cells for Metastatic Merkel Cell Carcinoma in Combination With MHC Class I Up-Regulation and the A

Brief Summary: This phase I/II trial studies the side effects and how well localized radiation therapy or recombinant interferon beta and avelumab with or without cellular adoptive immunotherapy works in treating patients with Merkel cell carcinoma that has spread to other parts of the body. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Interferon beta is a substance that can improve the body's natural response and may interfere with the growth of tumor cells. Monoclonal antibodies, such as avelumab, may help T lymphocytes kill tumor cells. For cellular adoptive immunotherapy, specific white blood cells are collected from the patient's blood and treated in the laboratory to recognize Merkel cell carcinoma. Infusing these cells back into the patient may help the body build an effective immune response to kill Merkel cell carcinoma. Giving localized radiation therapy or recombinant interferon beta and avelumab with or without cellular adoptive immunotherapy may be a better treatment for Merkel cell carcinoma.

Detailed Summary:

PRIMARY OBJECTIVES:

I. Assess and compare the safety and potential toxicities associated with treating patients with metastatic Merkel cell carcinoma (MCC) with either major histocompatibility complex (MHC) up regulation and programmed cell death 1 (PD1)-axis blockade (Group 1), or MHC up-regulation, PD1-axis blockade and adoptive transfer of Merkel cell polyoma virus (MCPyV) T antigen (TAg)-specific polyclonal autologous cluster of differentiation (CD)8+ T cells (Group 2).

II. Assess and compare the antitumor efficacy associated with treating patients with metastatic MCC with either MHC up-regulation and PD1-axis blockade (Group 1), or MHC up-regulation, PD1-axis blockade and adoptive transfer of MCPyV TAg-specific polyclonal autologous CD8+ T cells (Group 2).

SECONDARY OBJECTIVES:

I. Examine the in vivo persistence and, where evaluable, migration to tumor sites of adoptively transferred polyclonal CD8+ T cells targeting the MCPyV TAg (Group 2).

II. Examine the in vivo functional capacity of adoptively transferred polyclonal CD8+ T cells targeting the MCPyV Tag (Group 2).

III. Examine and compare evidence of epitope spreading with either MHC up-regulation and adoptive transfer of MHC up-regulation and PD1-axis blockade (Group 1), or MHC up regulation, PD1-axis blockade and adoptive transfer of MCPyV TAg-specific polyclonal autologous CD8+ T cells (Group 2).

OUTLINE: Patients who do not have a human leukocyte antigen (HLA) type for which T cells can be generated or for whom T cells cannot be generated for technical issues are assigned to Group 1. Patients who have an HLA type f
Sponsor: Fred Hutchinson Cancer Research Center

Current Primary Outcome:

• Evidence of response, based on median time to new metastasis [ Time Frame: Up to 4 years ]
• Incidence of adverse events, evaluated according to the current guidelines in NCI Common Toxicity Criteria version 4.0 [ Time Frame: Up to 12 months after the last infusion ]
  Evidence and nature of toxicity related to the treatment will be assessed and compared between groups.

Original Primary Outcome:

• Incidence of adverse events, evaluated according to the current guidelines in NCI Common Toxicity Criteria version 4.0 [ Time Frame: Up to 5 months after the last infusion ]
  Evidence and nature of toxicity related to the treatment will be assessed and compared between groups.
• Evidence of response, based on median time to new metastasis [ Time Frame: Up to 4 years ]

Current Secondary Outcome:

• Disease response, as assessed by Response Evaluation Criteria in Solid Tumors version 1.1 [ Time Frame: Up to 4 years ]
• Evidence of epitope spreading [ Time Frame: Up to 4 years ]
  Quantification of the overall recognition of the MCPyV T-antigen for each patient will likely be performed by testing the reactivity of whole PBMC before and at indicated timepoints after treatment to peptides 15 amino acids (aa) in length offset by 5 aa bases spanning the whole T-antigen protein to include both CD8 and CD4 responses regardless of the HLA type of the patient. The reactivity will be detected using IFN gamma secretion in a human IFN gamma enzyme-linked immunospot assay. Results will be presented as the number of spot forming cells/10^5 PBMCs.
• Functional capacity of transferred T cells (Group 2) [ Time Frame: Up to 4 years ]
  To evaluate the direct ex vivo function of the transferred cells, where possible, tetramer+ cells within collected peripheral blood mononuclear cells (PBMCs) will be evaluated for production of intracellular cytokines including interferon (IFN), tumor necrosis factor alpha and interleukin-2 in response to cognate antigen using an intracellular cytokine assay.
• MCC-specific survival [ Time Frame: Up to 4 years ]
• Persistence of transferred T cells in blood and tumor (Group 2) [ Time Frame: Up to 4 years ]

Original Secondary Outcome:

• Persistence of transferred T cells in blood and tumor (Group 2) [ Time Frame: Up to 4 years ]
• Functional capacity of transferred T cells (Group 2) [ Time Frame: Up to 4 years ]
  To evaluate the direct ex vivo function of the transferred cells, where possible, tetramer+ cells within collected peripheral blood mononuclear cells (PBMCs) will be evaluated for production of intracellular cytokines including interferon (IFN), tumor necrosis factor alpha and interleukin-2 in response to cognate antigen using an intracellular cytokine assay.
• Evidence of epitope spreading [ Time Frame: Up to 4 years ]
  Quantification of the overall recognition of the MCPyV T-antigen for each patient will likely be performed by testing the reactivity of whole PBMC before and at indicated timepoints after treatment to peptides 15 amino acids (aa) in length offset by 5 aa bases spanning the whole T-antigen protein to include both CD8 and CD4 responses regardless of the HLA type of the patient. The reactivity will be detected using IFN gamma secretion in a human IFN gamma enzyme-linked immunospot assay. Results will be presented as the number of spot forming cells/10^5 PBMCs.
• Disease response, as assessed by Response Evaluation Criteria in Solid Tumors version 1.1 [ Time Frame: Up to 4 years ]
• MCC-specific survival [ Time Frame: Up to 4 years ]

Dates:
Date Received: October 21, 2015
Date Started: November 2015
Date Completion:
Last Updated: February 15, 2017
Last Verified: February 2017