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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Collaborator:
Rockefeller University
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01456104
First received: October 18, 2011
Last updated: March 20, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Melanoma
Biological: Langerhans-type dendritic cells (a.k.a. Langerhans cells or LCs)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • safety [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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


Secondary Outcome Measures:
  • immunogenicity [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 9
Study Start Date: October 2011
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: vaccine
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).
Biological: Langerhans-type dendritic cells (a.k.a. Langerhans cells or LCs)
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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of melanoma, AJCC stage IIB, IIC, III, or IV (MIa), with histologic confirmation by the Department of Pathology at MSKCC.
  • Patients must be HLA-A*0201 positive, based on high resolution DNA level typing.
  • Expected survival of greater than 3 months.
  • Karnofsky performance status of 70 or higher
  • All patients should have undergone surgical treatment appropriate to their stage of disease
  • Patients may not have received chemotherapy, immunotherapy, or radiation within a minimum of 28 days (minimum of 42 days for nitrosoureas or mitomycin) before participation in this protocol.

Exclusion Criteria:

  • Pregnant or lactating women because of unknown risks to the fetus or infant.
  • Patients requiring systemic corticosteroids or comparable exogenous immunosuppressive agent(s) (no exclusion for use of NSAIDs).
  • Patients with a known immunodeficiency (e.g., infection with HTLV-1,2, HIV-1,2; etc.).
  • Patients with coexisting autoimmune diseases, except vitiligo.
  • Patients with baseline impairments of hematologic, hepatic, or renal function (CTCAE v4.0 > grade 1, ANC < 1500, hgb < 10.0 g/dl, plts < 75,000/ul, AST > 3x ULN, creatinine > 1.5xULN), all assessed within four weeks of study entry.
  • Patients with organ allografts.
  • Patients who are status post splenectomy or status post splenic irradiation.
  • Patients with a history of documented pre-existing retinal/choroidal disease.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01456104

Contacts
Contact: Jedd Wolchok, MD 646-888-2395
Contact: David Chung, MD, PhD 212-639-6617

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Jedd Wolochok, MD    646-888-2052      
Contact: David Chung, MD, PhD    212-639-6617      
Principal Investigator: James Young, MD         
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Rockefeller University
Investigators
Principal Investigator: James Young, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01456104     History of Changes
Other Study ID Numbers: 10-229
Study First Received: October 18, 2011
Last Updated: March 20, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
vaccine
stage IIB
stage IIC
stage III
stage IV (MIa)
Langerhans-type dendritic cells
Immune Responses
10-229

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on July 20, 2014