Chemotherapy Followed by Infusion of DMF5 Cells to Treat Metastatic Melanoma
- This study will use cells called DMF5 to treat patients with metastatic melanoma (melanoma that has spread beyond the primary tumor site).
- The DMF5 cells were first obtained from a tumor of a patient with melanoma with HLA-A201 tissue type. The tumor cells were grown in the laboratory, and when the laboratory-grown cells were given back to the patient, the patient's tumors shrank dramatically. In laboratory tests, DMF5 cells were also shown to shrink mouse melanoma tumors.
-To determine whether preparatory chemotherapy followed by infusion of DMF5 cells is a safe and effective for shrinking melanoma tumors.
-Patients with metastatic melanoma and tissue type HLA-A201 who are 18 years of age or older.
- Patients have a preparatory regimen of chemotherapy with cyclophosphamide and fludarabine followed by infusion of DMF5 cells and then high-dose interleukin. The chemotherapy, interleukin and cells are given intravenously (through a vein).
- Patients have frequent blood tests to look for the side effects and response to treatment.
- Patients may be asked to have a tumor biopsy (surgical removal of a small piece of tumor tissue) to examine the effects of treatment on the immune cells in the tumor.
- Patients have a physical examination, computed tomography (CT) of the chest, abdomen and pelvis and laboratory tests 4 to 6 weeks after treatment and then monthly to evaluate the tumor.
- The first group of patients participates in the Phase I portion of the study, called the dose escalation phase. This phase will determine the highest safe dose of DMF5 cells. There will be three dose levels of DMF5 cells, with the first patients enrolled getting the smallest dose and then increasing the dose when the preceding level has been shown to be safe.
- Patients in the Phase II portion of the study receive DMF5 cells at the highest dose found to be safe in Phase I, to test the effectiveness of the treatment.
Drug: DMF5 Melanoma Reactive TIL
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Study Using a Non-Myeloablative Lymphocyte Depleting Regimen of Chemotherapy Followed by Infusion of Allogeneic Tumor-Reactive Lymphocyte Cell Line DMF5 in Metastatic Melanoma|
- Number of Participants With an Objective Clinical Tumor Regression Response According to RECIST Criteria [ Time Frame: 44 days ] [ Designated as safety issue: No ]Response is determined by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is the disappearance of all target lesions, partial response (PR) is at least a 30% decrease in the target lesions, progression (PD) is at least a 20% increase in the target lesions or appearance of one or more new lesions, and stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
- Number of Participants With Adverse Events [ Time Frame: 44 days ] [ Designated as safety issue: Yes ]Here are the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.
- Number of Participiants With In-vivo Survival of Infused Cells [ Time Frame: 44 days ] [ Designated as safety issue: No ]In-vivo survival of infused cells is determined by analysis of the sequence of the variable region of the T cell receptor or flow cytometry (FACS).
|Study Start Date:||August 2007|
|Study Completion Date:||October 2010|
|Primary Completion Date:||October 2010 (Final data collection date for primary outcome measure)|
Experimental: Metastatic Melanoma
Melanoma that has invaded deep into the skin, lymph nodes, or other parts of the body.
Drug: DMF5 Melanoma Reactive TIL
given intravenously over 20-30 minutes (between 1 x 10^9 and 1 x 10^11 lymphocytes) after expansion in interleukin-2 and OKT-3Drug: Cyclophosphamide
60 mg/kg/day x 2 days intravenously
Other Names:Drug: Fludarabine
25 mg/m^2/day intravenously x 5 days
Other Name: FludaraDrug: Aldesleukin
720,000 IU/kg/dose intravenously every 8 hours for up to 15 doses
Other Name: Proleukin
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|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Steven Rosenberg, M.D.||National Cancer Institute, National Institutes of Health|