Clinical trial NCT01456104: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Melanoma
Keywords: vaccine
stage IIB
stage IIC
stage III
stage IV (MIa)
Langerhans-type dendritic cells
Immune Responses
10-229
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: Rockefeller University
First posted: 2011-10-20
Enrollment: 9
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: safety
timeFrame: 1 year
measure: toxicity
timeFrame: 1 year
Secondary outcomes:
measure: immunogenicity
timeFrame: 1 year
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: James Young, MD
role: PRINCIPAL_INVESTIGATOR
References: