A Phase 1 interventional study of Laboratory Biomarker Analysis and Pharmacological Study in Head and Neck Squamous Cell Carcinoma, Recurrent Head and Neck Carcinoma and Recurrent Non-Small Cell Lung Carcinoma, sponsored by National Cancer Institute (NCI). Completed at 5 sites in United States. Open to participants aged 19 Years and older. Per ClinicalTrials.gov, last updated 2017-09-15.
Sponsored by National Cancer Institute (NCI) · Phase 1, Interventional, and Treatment
This phase I trial studies the side effects and best dose of recombinant interleukin-15 in treating patients with melanoma, kidney cancer, non-small cell lung cancer, or head and neck cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment. Recombinant interleukin-(IL)15 is a biological product, a protein, made naturally in the body and when made in the laboratory may help stimulate the immune system in different ways and stop tumor cells from growing.
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) of recombinant human IL15 (rhIL15) administered subcutaneously.
SECONDARY OBJECTIVES:
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.
6,745 studies on the registry are indexed under Carcinoma; 1,163 are open to participants now.
This study's enrollment of 20 is below the median of 45 across 5,174 interventional studies indexed under Carcinoma.
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Prior therapy requirements:
Exclusion Criteria:
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
Correlative studies
Correlative studies
Given SC
Also known as: IL15, Interleukin 15, rhIL-15, rIL15
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
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).
Time frame: Up to 6 months
Change in NK cell function measured using flow cytometric analysis of cytokine (IFN-y) secretion and expression of degranulation marker CD107a
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.
Time frame: Baseline to day 15
Change in presence of auto-antibodies, assessed by ELISA
The number and percentage of patients developing auto-antibodies to IL15 will be tabulated by dose cohort.
Time frame: Baseline to day 4 of week 2
Change in T cell responses to non- physiologic stimuli including PMA
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.
Time frame: Baseline to day 4 of week 2
Change in T cell subset response to recall viral antigens including CMV and influenza A virus, determined by enzyme-linked immunosorbent spot assay
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.
Time frame: Baseline to day 4 of week 2
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
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.
Time frame: Baseline to day 15
ORR based on RECIST criteria
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.
Time frame: Up to day 56 (after 2 courses)
Serum PK of IL15 and IL15 receptor-alpha, assessed by enzyme linked immunosorbent assay (ELISA)
IL15 and IL15 receptor-alpha levels will be plotted over time for each dose group.
Time frame: Pre-dose, and 10 minutes, 1, 4, and 24 hours after administration
Total white blood cell count, monitored daily during treatment
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).
Time frame: Up to 6 months
This study is completed, as verified in Sep 2017. You cannot join it, but the record below documents what was studied.
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National Cancer Institute (NCI)