Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

All Drugs and Chemicals

Anti-Infective Agents

Vaccines

Carbamide Peroxide

This is a single-arm phase I trial in patients with AJCC stage IIB, IIC, III, and IV (MIa) melanoma in which autologous human Langerhans-type dendritic cells (CD34+hematopoietic progenitor cell (HPC)-derived Langerhans cells, or LCs) will be electroporated with mRNA encoding full-length murine tyrosinase-related peptide 2 (TRP2). LCs will also be loaded with control antigens (HLA-A\*0201-restricted flu matrix peptide).

Patients will receive a total of 5 vaccinations, comprising a primary immunization followed by four boosters at 3 week intervals with a window of ± 4 days. Vaccines will be dosed at 10x106 LCs per vaccine x 5.

Langerhans-type dendritic cells (a.k.a. Langerhans cells or LCs)

James Young, MD

This study is being done to see if the investigators can help the immune system to work against melanoma.

A dendritic cell is another type of white blood cell. It has most, if not all, of the proteins needed to make T cells work to destroy cancer cells. However, dendritic cells do not normally have the cancer proteins on their surface. The challenge then is to combine the antigens with dendritic cells to make a vaccine. The investigators think that the body's T cells might then react against the tumor and help destroy it.

This study will see if altered dendritic cells will make T cells work against tumor cells. The dendritic cells will be made in a lab and will carry the antigens. These cells then will be injected under the skin.

In this study, the investigators are trying to help the body make a stronger immune response against the cancer. The patient will get the same kind of dendritic cell vaccine used in the earlier study, but with one major difference. The dendritic cells will contain messenger-RNA (mRNA). Cells use mRNA to make proteins. The mRNA will be put into dendritic cells by a laboratory method called electroporation. The mRNA is never given to the patient directly. This mRNA will help the dendritic cell make a tumor antigen like what the cancer expresses. The dendritic cell can then put this tumor antigen on its surface so that the body could make a stronger immune response against the tumor.

Immune Responses to Autologous Langerhans-type Dendritic Cells Electroporated With mRNA Encoding a Tumor-associated Antigen in Patients With Malignancy: A Single-arm Phase I Trial in Melanoma

Toxicity will be graded according to standard NCI/CTEP toxicity criteria. This protocol will use the Common Terminology Criteria for Adverse Events (CTCAE) v4.0

Toxicity will be graded according to standard NCI/CTEP toxicity criteria. This protocol will use the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Due to the nature of this treatment and the expected mild erythema and occasional pruritus, only grade 3-4 toxicities will be evaluated

For this study, the vaccine is considered promising if more than four out of the nine patients have an immunologic response (e.g., tetramer staining and intracellular cytokine secretion assays). Samples taken after vaccination will be considered positive for response if they are higher than the pre-vaccination values by at least two standard deviations. For each patient, the standard deviation of the background (calculated using triplicates) will be computed, and a positive will be defined as greater than two times this value.

Rockefeller University

Memorial Sloan Kettering Cancer Center

Symptoms and General Pathology

Infections

Blood and Lymph Conditions

Immune System Diseases

Syndrome

Mycoses

Lymphoma

Lymphoma, T-Cell

Lymphoma, T-Cell, Peripheral

Mycosis Fungoides

Lymphoma, T-Cell, Cutaneous

Sezary Syndrome

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Communicable Diseases

Bacterial Infections

Bacterial Infections and Mycoses

Lymphosarcoma

Peripheral T-cell Lymphoma

Cutaneous T-cell Lymphoma

Larisa J. Geskin, M.D.

This is an in vitro evaluation of cutaneous T-cell lymphoma using patients' blood and tissue to evaluate immune responses related to identified tumor populations and dendritic/CD 8 cells.

This is an in vitro evaluation of cutaneous T-cell lymphoma using patients blood and tissue to evaluate immune responses related to identified tumor populations and dendritic/ CD 8 cells with the following objectives:

* Objective I: Evaluate the feasibility of the preparation of dendritic cells (DCs), CD8 and Sezary cells (all CD4 positive) in vitro, obtained from the buffy coats or a skin biopsy from an area with tumor involvement of subjects with cutaneous t-cell lymphoma (CTCL) and Sezary syndrome (leukemic stage of CTCL) undergoing an approved FDA therapy, extracorporeal photopheresis (ECP).
* Objective II: Evaluate antigen loading of the DCs.
* Objective III: Test the functional capacities of the DCs derived from CTCL subjects to overcome immune tolerance to the tumor cells ex-vivo, by using modified Elispot assay in conjunction with Granzyme B Elispot assay as a measurement of cytotoxicity.

In Vitro Evaluation of Immune Responses in Cutaneous T-Cell Lymphoma (CTCL)

In Vitro Evaluation of Immune Responses in CTCL

Evaluate the feasibility of the preparation of dendritic cells (DCs), CD8 and Sezary cells (all CD4 positive) in vitro, obtained from the buffy coats or a skin biopsy from an area with tumor involvement of subjects with cutaneous t-cell lymphoma (CTCL) and Sezary syndrome (leukemic stage of CTCL)

Functional DCs can be isolated and effectively loaded with the malignant cells by several methods (coculture and fusion)

University of Pittsburgh

Associate Professor of Dermatology

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Immune Responses to Autologous Langerhans-type Dendritic Cells Electroporated With mRNA Encoding a Tumor-associated Antigen in Patients With Malignancy: A Single-arm Phase I Trial in Melanoma	NCT01456104	Melanoma	Langerhans-type...	-	Memorial Sloan Kettering Cancer Center
In Vitro Evaluation of Immune Responses in Cutaneous T-Cell Lymphoma (CTCL)	NCT00177190	Cutaneous T-cel... Sezary Syndrome Mycosis Fungoid...		18 Years -	University of Pittsburgh
Immune Responses to Autologous Langerhans-type Dendritic Cells Electroporated With mRNA Encoding a Tumor-associated Antigen in Patients With Malignancy: A Single-arm Phase I Trial in Melanoma	NCT01456104	Melanoma	Langerhans-type...	-	Memorial Sloan Kettering Cancer Center
In Vitro Evaluation of Immune Responses in Cutaneous T-Cell Lymphoma (CTCL)	NCT00177190	Cutaneous T-cel... Sezary Syndrome Mycosis Fungoid...		18 Years -	University of Pittsburgh

Spots Global Cancer Trial Database for immune responses