Clinical Trial: Phase II Study of Short-Term Cultured Anti-Tumor Autologous Lymphocytes After Lymphocyte-Depleting Chemotherapy in Metastatic Melanoma

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase II Study Using Short-Term Cultured Anti-Tumor Autologous Lymphocytes Following a Lymphocyte Depleting Regimen in Metastatic Melanoma

Brief Summary:

Background:

• Most therapeutic therapies for metastatic melanoma have focused on the ability of T-cell lymphocytes to kill cells of tumors.
• An adaptive cell transfer therapy has been pioneered, in which cells are grown for a short time in the laboratory. The way they are grown may have a better effect in a patient's body than do other cells that are cultured for a longer time.

Objectives:

• To determine whether tumor-infiltrating lymphocytes (TIL) can be put in cells removed from patients' tumors or blood and then reinfused, with the purpose of shrinking tumors.
• To evaluate safety and effectiveness of the treatment.

Eligibility:

• Patients 18 years of age or older with metastatic cancer melanoma (cancer that has spread beyond the original site).
• Patient's leukocyte antigen type is human leukocyte antigens (HLA-A) 0201.

Design:

-Patients undergo the following procedures:

• Leukapheresis (on two occasions). This is a method of collecting large numbers of white blood cells. The cells obtained in the first leukapheresis procedure are grown in the laboratory, and the TIL cells (called young TIL cells) are inserted into the cells using an inactivated (harmless) virus in a process called retroviral transduction. Cells collected in the second leukapheresis procedure are used to evaluate the effe
  

  Detailed Summary:

  Background:

  • Tumor Infiltrating Lymphocytes (TIL) can mediate the regression of bulky metastatic melanoma when administered to an autologous patient with high dose (HD) IL-2 following a non-myeloablative (NMA) but lymphodepleting chemotherapy preparative regimen.
  • Clinical investigations and preclinical animal models have demonstrated that less time in culture, longer telomeres, and a less differentiated lymphocyte phenotype are associated with TIL that are capable of mediating objective clinical responses and persisting long term in the host.
  • Previous methods for generating TIL require screening for anti-tumor specificity using gamma-interferon (IFN) production by the TIL. However, in vitro screening depends on autologous tumor reagents that are often unavailable; and gamma-IFN release in vitro may not be the best correlate to in vivo efficacy. Additionally, this method necessitates long in vitro culture times (44 days), and therefore reduces the clonal heterogeneity of TIL cultures, and results in TIL cultures with shorter telomere lengths and phenotypes that are skewed toward a more differentiated phenotype.
  • In Surgery Branch pre-clinical experiments, we evaluated a method for rapidly generating young TIL from melanoma tumors with optimal phenotypic characteristics.

  Objectives:

  • In cohort 1, to determine the ability of autologous TIL cells infused after minimal in vitro culture in conjunction with high dose aldesleukin (IL-2) following a non-myeloablative lymphodepleting preparative regimen to mediate tumor regression in patients with metastatic melanoma.
  • In cohort 2
    Sponsor: National Cancer Institute (NCI)
    

    Current Primary Outcome:

    • Clinical Response [ Time Frame: every 1-3 months until disease progression. Total length of time -8/7/2007 to 9/27/2012 ]
      Clinical response is defined as complete response (CR)- a disappearance of all target lesions, partial response (PR) - at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Progression (PD)- at least a 20% increase in the sum of the LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable disease (SD) - neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD.
    • Toxicity [ Time Frame: 5 years ]
      Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
    
    
    

    Original Primary Outcome:

    • Tumor regression
    • Toxicity
    
    
    

    Current Secondary Outcome:
    
    

    Original Secondary Outcome:

    • Rate of lymphocyte cell repopulation
    • In vitro immunological correlates that predict in vivo persistence and clinical response
    
    
    Information By: National Institutes of Health Clinical Center (CC)
    

    Dates:
    Date Received: August 6, 2007
    Date Started: June 2007
    Date Completion:
    Last Updated: May 29, 2013
    Last Verified: May 2013