Clinical Trial: Chemotherapy Followed by Infusion of DMF5 Cells to Treat Metastatic Melanoma

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

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

Brief Summary:

Background:

  • 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.

Objectives:

-To determine whether preparatory chemotherapy followed by infusion of DMF5 cells is a safe and effective for shrinking melanoma tumors.

Eligibility:

-Patients with metastatic melanoma and tissue type HLA-A201 who are 18 years of age or older.

Design:

  • 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 treatm

    Detailed Summary:

    Background:

    In previous trials in the Surgery Branch, a 51 percent objective response rate has been observed in heavily pre-treated patients with metastatic melanoma undergoing adoptive cell transfer therapy utilizing a non-myeloablative preparative regimen followed by administration of autologous tumor-reactive lymphocytes and subsequent treatment with high-dose aldesleukin.

    However, in patients with metastatic melanoma undergoing metastasectomy, recovery of adequate numbers of tumor specific T lymphocytes from surgical specimens is possible in approximately half of all patients, thus limiting the application of adoptive cell transfer therapy.

    Murine models performed in the Surgery Branch have demonstrated solid tumor regression in mice treated with allogeneic tumor specific T cells combined with a preinfusion lymphodepleting regimen.

    We have identified a tumor specific lymphocyte cell line (DMF5) used previously in an autologous adoptive cell transfer protocol that was associated with an objective clinical response in that patient.

    In subsequent preclinical testing of this lymphocyte population, we have demonstrated high specificity against HLA-A 0201 positive melanoma cell lines as well as the common shared melanocyte differentiation antigen MART-1:27-35. We have expanded this lymphocyte population to provide up to 30 individual allogeneic cell transfers to HLAA 0201 positive patients with metastatic melanoma.

    In this trial we want to test our hypothesis that objective tumor regression can be achieved with the DMF5 allogeneic T-cell product using a non-myeloablative regimen followed by cell transfer and high-dose aldesleuki
    Sponsor: National Cancer Institute (NCI)

    Current Primary Outcome:

    • Number of Participants With an Objective Clinical Tumor Regression Response According to RECIST Criteria [ Time Frame: 44 days ]
      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 ]
      Here are the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.


    Original Primary Outcome: Clinical response according to RECIST criteria and toxicity.

    Current Secondary Outcome: Number of Participiants With In-vivo Survival of Infused Cells [ Time Frame: 44 days ]

    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).


    Original Secondary Outcome: Determine the rate of repopulation of young TIL cells and establish correlates that predict in vivo persistence and clinical response.

    Information By: National Institutes of Health Clinical Center (CC)

    Dates:
    Date Received: June 17, 2009
    Date Started: August 2007
    Date Completion:
    Last Updated: October 18, 2012
    Last Verified: October 2012