This phase I/II trial studies how well genetically modified therapeutic autologous lymphocytes (patient's own white blood cells) followed by aldesleukin work in treating patients with stage III melanoma or melanoma that has spread to other places in the body (metastatic). Placing chemokine (C-X-C motif) receptor 2 (CXCR2) and nerve growth factor receptor (NGFR) into lymphocytes (white blood cells) may help the body build an immune response to kill melanoma cells. Aldesleukin may enhance this effect by stimulating white blood cells to kill more melanoma cells. Giving genetically modified therapeutic autologous lymphocytes together with aldesleukin may be a better treatment for melanoma.
PRIMARY OBJECTIVES: I. To assess the feasibility and safety of CXCR2 and NGFR transduced tumor-infiltrating lymphocytes (TIL) for treating metastatic malignant melanoma. SECONDARY OBJECTIVES: I. Determine whether CXCR2 transduction enhances the ability of TIL to migrate to melanoma tumors. II. Determine the levels of CXCL1 and CXCL8 chemokines produced by melanoma tumors and assess whether this correlates with the tumor localization of CXCR2 transduced TIL. III. Characterize the clinical response and correlate with migration of CXCR2 transduced TIL to the tumor and levels of CXCL1 and CXCL8 at the tumor site. OUTLINE: Patients receive cyclophosphamide intravenously (IV) over 2 hours on days -7 and -6, fludarabine phosphate IV daily over 15-30 minutes on days -5 to -1, and CXCR2-transduced autologous TIL and NGFR-transduced autologous TIL IV over up to 4 hours on day 0. Patients then receive high-dose aldesleukin IV over 15 minutes every 8-16 hours on days 1-5 (up to 15 doses) and 22-26 (up to 15 doses). After completion of study treatment, patients are followed up at weeks 6 and 12, every 3 months for a year, and then annually for up to 15 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
Given IV
Given IV
Given IV
Given IV
Correlative studies
Given IV
Ancillary studies
M D Anderson Cancer Center
Houston, Texas, United States
Number of Participants With Immune-Related Response
Response will be defined as a 50% or greater decrease in the tumor's linear dimension post treatment, compared to baseline. Response will be evaluated by positron emission tomography or computed tomography imaging.
Time frame: Up to 1 year
Number of Participants With Adverse Events Defined as Possible Grade 3 or Worse Toxicities
Possible grade 3 or worse toxicities not normally associated with lymphodepletion and high dose IL-2 will be reported.
Time frame: Up to 8 weeks
CXCR2 Transduction
Determine whether CXCR2 transduction enhances the ability of TIL to migrate to melanoma tumors. his is a statistical version of the intuitive idea that, if the TIL methodology works as designed and the genetically transduced T-cells differentially recognize the cancer cell cytokines, then the ratio of post- and pre-treatment ratios RR = RY/RX should be larger than 1.
Time frame: At infusion
CXCL1 and CXCL8 Chemokines Produced
Determine the levels of CXCL1 and CXCL8 chemokines produced by melanoma tumors and assess whether this correlates with the tumor localization of CXCR2 transduced TIL
Time frame: At infusion
Characterize the Clinical Response and Correlate With Migration of CXCR2 Transduced TIL to the Tumor and Levels of CXCL1 and CXCL8 at the Tumor Site.
Time frame: At infusion
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