Laboratory-Treated T Cells and Ipilimumab in Treating Patients With Metastatic Melanoma
Stage IV Melanoma
Other: immunohistochemistry staining method
Genetic: polymerase chain reaction
Other: immunoenzyme technique
Biological: therapeutic allogeneic cytotoxic T lymphocytes
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Single Blind
Primary Purpose: Treatment
|Official Title:||Phase I/II Study of Cellular Adoptive Immunotherapy Using Autologous CD8+ Antigen-Specific T Cells and Anti-CTLA4 For Patients With Metastatic Melanoma|
- Numeric frequency and functional persistence of transferred CTL [ Time Frame: Up to 6 months post-infusion ] [ Designated as safety issue: No ]Determined using peptide major histocompatibility complex (MHC)-tetramer analysis or specific CDR3 T-cell-receptor (TCR) quantitative polymerase chain reaction (PCR) of transferred CTL if necessary. The function of transferred CTL will be determined by intracellular cytokine staining of tetramer+ CD8+ cells following in vitro stimulation.
- Toxicity assessment of study treatment, assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0 [ Time Frame: Up to 6 months post-infusion ] [ Designated as safety issue: Yes ]
- Responses to non-targeted T cell antigens [ Time Frame: Up to 1 year following T cell infusion and/or at the time of observed partial or complete clinical response ] [ Designated as safety issue: No ]Blood samples taken will be analyzed for the induction of non-targeted T cell responses. Two approaches will be used: tetramer analysis and enzyme-linked immunosorbent spot (ELISPOT) assay.
|Study Start Date:||February 2009|
|Study Completion Date:||October 2013|
|Primary Completion Date:||September 2013 (Final data collection date for primary outcome measure)|
Experimental: Treatment (laboratory-treated T cells and ipilimumab)
Patients receive cyclophosphamide IV on day -2, therapeutic allogeneic cytotoxic T lymphocytes IV over 30-60 minutes on day 0, low-dose aldesleukin SC BID on days 0-13, and ipilimumab IV over 90 minutes on days 1, 22, 43, and 64 in the absence of disease progression or unacceptable toxicity.
Other Names:Drug: cyclophosphamide
Other Names:Procedure: biopsy
Optional correlative studies
Other Name: biopsiesBiological: aldesleukin
Other Names:Other: immunohistochemistry staining method
Other Name: immunohistochemistryGenetic: polymerase chain reaction
Other Name: PCROther: immunoenzyme technique
Other Name: immunoenzyme techniquesBiological: therapeutic allogeneic cytotoxic T lymphocytes
Other Name: therapeutic allogeneic CTLs
I. Evaluate the safety and efficacy of adoptively transferred cytotoxic lymphocytes (CTL) targeting melanoma tumors combined with anti-CTLA4.
II. Evaluate the influence of anti-CTLA4 (ipilimumab) on the duration of in vivo persistence and anti-tumor efficacy achieved following adoptive transfer of antigen-specific CTL.
I. Evaluate the influence of anti-CTLA4 on the induction of T cells to non-targeted tumor-associated antigens (antigen-spreading) following adoptive transfer antigen-specific CTL, and the correlation of these responses with clinical outcome.
Patients receive cyclophosphamide intravenously (IV) on day -2, therapeutic allogeneic cytotoxic T lymphocytes IV over 30-60 minutes on day 0, low-dose aldesleukin subcutaneously (SC) twice daily (BID) on days 0-13, and ipilimumab IV over 90 minutes on days 1, 22, 43, and 64 in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00871481
|United States, Washington|
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|
|Seattle, Washington, United States, 98109|
|Principal Investigator:||Aude Chapuis||Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|