Recombinant Interleukin-15 in Treating Patients With Advanced Melanoma, Kidney Cancer, Non-small Cell Lung Cancer, or Squamous Cell Head and Neck Cancer
|ClinicalTrials.gov Identifier: NCT01727076|
Recruitment Status : Completed
First Posted : November 15, 2012
Last Update Posted : September 15, 2017
|Condition or disease||Intervention/treatment||Phase|
|Head and Neck Squamous Cell Carcinoma Recurrent Head and Neck Carcinoma Recurrent Non-Small Cell Lung Carcinoma Recurrent Renal Cell Carcinoma Recurrent Skin Carcinoma Stage III Renal Cell Cancer Stage IIIA Cutaneous Melanoma AJCC v7 Stage IIIA Non-Small Cell Lung Cancer AJCC v7 Stage IIIB Cutaneous Melanoma AJCC v7 Stage IIIB Non-Small Cell Lung Cancer AJCC v7 Stage IIIC Cutaneous Melanoma AJCC v7 Stage IV Cutaneous Melanoma AJCC v6 and v7 Stage IV Non-Small Cell Lung Cancer AJCC v7 Stage IV Renal Cell Cancer||Other: Laboratory Biomarker Analysis Other: Pharmacological Study Biological: Recombinant Human Interleukin-15||Phase 1|
I. To determine the maximum tolerated dose (MTD) of recombinant human IL15 (rhIL15) administered subcutaneously.
I. To determine the effect of the dose schedules of rhIL15 on the number and phenotype of peripheral blood mononuclear cells including: total white blood cell count; absolute lymphocyte count (ALC); and total number of T cells and natural killer (NK) cells, as well as activated T cells, T cell subsets and NK cell subsets.
II. To determine the effects of the dose schedules of rhIL15 on the function of peripheral blood mononuclear cells including: T cell subset response to recall viral antigens including cytomegalovirus (CMV) and influenza A virus; T cell responses to non-physiologic stimuli including: phytohemagglutinin (PHA); and NK cell cytokine (interferon gamma [IFN-y]) secretion and degranulation by cluster of differentiation 107a (CD107a) expression.
III. To assess tumor response rate by objective response rate (ORR). IV. To assess the immunogenicity, pharmacokinetic (PK) and pharmacodynamic (PD) profiles of National Cancer Institute (NCI) rhIL15.
OUTLINE: This is a dose-escalation study.
Patients receive recombinant interleukin-15 subcutaneously (SC) daily on days 1-5 of weeks 1 and 2. Treatment repeats every 28 days (4 weeks) for up to 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 24 weeks.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 Study of Recombinant Human IL15 (rhIL15) in Adults With Advanced Solid Tumors: Melanoma, Renal Cell, Non-Small Cell Lung and Squamous Cell Head and Neck Cancer|
|Actual Study Start Date :||February 15, 2013|
|Actual Primary Completion Date :||June 30, 2016|
|Actual Study Completion Date :||June 30, 2016|
Experimental: Treatment (recombinant interleukin-15)
Patients receive recombinant interleukin-15 SC daily on days 1-5 of weeks 1 and 2. Treatment repeats every 28 days (4 weeks) for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Biological: Recombinant Human Interleukin-15
- MTD defined as the next lower dose in which 1 or more patients experiences a dose limiting toxicity defined as grade 3 or 4 toxicity graded according to the NCI Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: 28 days ]
- ALC, monitored daily during treatment [ Time Frame: Up to 6 months ]The absolute increase in each cell subset as well as the variance in change across each dose level (mean, median, and SE/SD will be reported for each dose level and ALC, circulating NK count, and circulating CD4/CD8 cell counts).
- Change in NK cell function measured using flow cytometric analysis of cytokine (IFN-y) secretion and expression of degranulation marker CD107a [ Time Frame: Baseline to day 15 ]The absolute change in responses for each patient will be calculated by subtracting the SFC/million PBMC at day 11 from the SFC/million PBMC at baseline for each antigen.
- Change in presence of auto-antibodies, assessed by ELISA [ Time Frame: Baseline to day 4 of week 2 ]The number and percentage of patients developing auto-antibodies to IL15 will be tabulated by dose cohort.
- Change in T cell responses to non- physiologic stimuli including PMA [ Time Frame: Baseline to day 4 of week 2 ]The absolute change in responses for each patient will be calculated by subtracting the SFC/million PBMC at day 11 from the SFC/million PBMC at baseline for each antigen.
- Change in T cell subset response to recall viral antigens including CMV and influenza A virus, determined by enzyme-linked immunosorbent spot assay [ Time Frame: Baseline to day 4 of week 2 ]The absolute change in responses for each patient will be calculated by subtracting the spot forming cells (SFC)/million peripheral blood mononuclear cell (PBMC) at day 11 from the SFC/million PBMC at baseline for each antigen.
- Change in total number of T cells and NK cells, as well as activated T cells, T cell subsets, and NK cell subsets, assessed by flow cytometric analysis of peripheral blood mononuclear cells [ Time Frame: Baseline to day 15 ]The percentage of cells positive for the marker and/or mean fluorescence intensity (MFI) at time points after rhIL15 administration will be compared to baseline and the change will be calculated as %after/ %baseline or MFI after/ MFI baseline.
- ORR based on RECIST criteria [ Time Frame: Up to day 56 (after 2 courses) ]Percentages and exact 2-sided 95% confidence intervals of the numbers in each of the overall response categories (complete response, partial response, stable disease and progressive disease) will be calculated for each dose cohort.
- Serum PK of IL15 and IL15 receptor-alpha, assessed by enzyme linked immunosorbent assay (ELISA) [ Time Frame: Pre-dose, and 10 minutes, 1, 4, and 24 hours after administration ]IL15 and IL15 receptor-alpha levels will be plotted over time for each dose group.
- Total white blood cell count, monitored daily during treatment [ Time Frame: Up to 6 months ]The absolute increase in each cell subset as well as the variance in change across each dose level (mean, median, and standard error [SE]/standard deviation [SD] will be reported for each dose level and absolute lymphocyte count [ALC], circulating NK count, and circulating CD4/CD8 cell counts).
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01727076
|United States, California|
|Stanford Cancer Institute Palo Alto|
|Palo Alto, California, United States, 94304|
|United States, Maryland|
|National Institutes of Health Clinical Center|
|Bethesda, Maryland, United States, 20892|
|United States, Minnesota|
|University of Minnesota/Masonic Cancer Center|
|Minneapolis, Minnesota, United States, 55455|
|United States, Washington|
|Seattle Cancer Care Alliance|
|Seattle, Washington, United States, 98109|
|United States, Wisconsin|
|University of Wisconsin Hospital and Clinics|
|Madison, Wisconsin, United States, 53792|
|Principal Investigator:||Jeffrey Miller||Cancer Immunotherapy Trials Network|