Recombinant Interleukin-15 in Treating Patients With Advanced Melanoma, Kidney Cancer, Non-Small Cell Lung Cancer, or Squamous Cell Head and Neck Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01727076
First received: November 12, 2012
Last updated: July 11, 2014
Last verified: April 2014
  Purpose

This phase I trial studies the side effects and best dose of recombinant interleukin-15 in treating patients with advanced melanoma, kidney cancer, non-small cell lung cancer, or head and neck cancer. Recombinant interleukin-15 may kill tumor cells by stopping blood flow to the tumor and by stimulating white blood cells to kill melanoma, kidney, non-small cell lung, and squamous cell head and neck cancer cells.


Condition Intervention Phase
Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma
Recurrent Melanoma
Recurrent Metastatic Squamous Neck Cancer With Occult Primary
Recurrent Non-small Cell Lung Cancer
Recurrent Renal Cell Cancer
Recurrent Salivary Gland Cancer
Recurrent Squamous Cell Carcinoma of the Hypopharynx
Recurrent Squamous Cell Carcinoma of the Larynx
Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity
Recurrent Squamous Cell Carcinoma of the Nasopharynx
Recurrent Squamous Cell Carcinoma of the Oropharynx
Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Recurrent Verrucous Carcinoma of the Larynx
Recurrent Verrucous Carcinoma of the Oral Cavity
Stage III Renal Cell Cancer
Stage III Salivary Gland Cancer
Stage III Squamous Cell Carcinoma of the Hypopharynx
Stage III Squamous Cell Carcinoma of the Larynx
Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage III Squamous Cell Carcinoma of the Nasopharynx
Stage III Squamous Cell Carcinoma of the Oropharynx
Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Stage III Verrucous Carcinoma of the Larynx
Stage III Verrucous Carcinoma of the Oral Cavity
Stage IIIA Melanoma
Stage IIIA Non-small Cell Lung Cancer
Stage IIIB Melanoma
Stage IIIB Non-small Cell Lung Cancer
Stage IIIC Melanoma
Stage IV Melanoma
Stage IV Non-small Cell Lung Cancer
Stage IV Renal Cell Cancer
Stage IV Squamous Cell Carcinoma of the Hypopharynx
Stage IV Squamous Cell Carcinoma of the Nasopharynx
Stage IVA Salivary Gland Cancer
Stage IVA Squamous Cell Carcinoma of the Larynx
Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage IVA Squamous Cell Carcinoma of the Oropharynx
Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Stage IVA Verrucous Carcinoma of the Larynx
Stage IVA Verrucous Carcinoma of the Oral Cavity
Stage IVB Salivary Gland Cancer
Stage IVB Squamous Cell Carcinoma of the Larynx
Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage IVB Squamous Cell Carcinoma of the Oropharynx
Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Stage IVB Verrucous Carcinoma of the Larynx
Stage IVB Verrucous Carcinoma of the Oral Cavity
Stage IVC Salivary Gland Cancer
Stage IVC Squamous Cell Carcinoma of the Larynx
Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage IVC Squamous Cell Carcinoma of the Oropharynx
Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Stage IVC Verrucous Carcinoma of the Larynx
Stage IVC Verrucous Carcinoma of the Oral Cavity
Tongue Cancer
Biological: recombinant interleukin-15
Other: pharmacological study
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • MTD defined as the next lower dose in which 1 or more patients experiences a dose limiting toxicity (DLT) defined as grade 3 or 4 toxicity graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Total white blood cell (WBC) count [ Time Frame: Up to 4 months ] [ Designated as safety issue: No ]
    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).

  • Absolute lymphocyte count [ Time Frame: Up to 4 months ] [ Designated as safety issue: No ]
    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 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 (PBMCs) [ Time Frame: Baseline to day 15 ] [ Designated as safety issue: No ]
    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.

  • T cell subset response to recall viral antigens including CMV and influenza A virus, determined by enzyme-linked immunosorbent spot (ELISPOT) assay [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    The absolute change in responses for each patient will be calculated by subtracting the spot forming cells (SFC)/million PBMC at day 11 from the SFC/million PBMC at baseline for each antigen.

  • T cell subset response to recall viral antigens including CMV and influenza A virus, determined by ELISPOT assay [ Time Frame: Day 11 ] [ Designated as safety issue: No ]
    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.

  • T cell responses to non- physiologic stimuli including PMA [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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.

  • T cell responses to non- physiologic stimuli including PMA [ Time Frame: Day 11 ] [ Designated as safety issue: No ]
    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 NK cell function measured using flow cytometric analysis of cytokine secretion and expression of degranulation marker CD107a [ Time Frame: Baseline to day 15 ] [ Designated as safety issue: No ]
    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.

  • ORR based on RECIST criteria [ Time Frame: Up to day 56 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Pre-dose, 10 minute, 1, 4, and 24 hours ] [ Designated as safety issue: No ]
    IL15 and IL15 receptor-alpha levels will be plotted over time for each dose group. The number and percentage of patients developing auto-antibodies to IL15 will be tabulated by dose cohort.

  • Presence of auto-antibodies, assessed by ELISA [ Time Frame: Up to day 11 ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: February 2013
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (recombinant interleukin-15)
Patients receive recombinant interleukin-15 SC daily on days 1-5 and 8-12. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Biological: recombinant interleukin-15
Given SC
Other Names:
  • IL15
  • interleukin 15
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of recombinant human IL15 (recombinant interleukin-15) (rhIL15) administered subcutaneous.

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), 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 and 8-12. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 24 weeks.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histological or cytological confirmed malignancy in the following disease groups: melanoma, non-small cell lung carcinoma, renal cell carcinoma or squamous cell head and neck carcinoma, for which no standard effective or curative options are available
  • Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  • Documented evidence of disease progression during 6 month period prior to the time of enrollment
  • Prior therapy requirements:

    • At least >= 1 prior completed chemotherapy regimen including biological, immunological or targeted therapy
    • At least 4 weeks from last dose of prior chemotherapy with resolution of the acute toxic effects of the therapy
    • At least 2 weeks from completion of prior radiation therapy
    • At least 4 weeks from last dose of prior investigational therapy
    • Not receiving any current anti-cancer therapy
    • At least 4 weeks from last dose of interferon or interleukin (IL)-2 therapy
    • At least 8 weeks from completion of antibody therapy with anti-checkpoint antibodies, such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) and anti-programmed cell death 1 (PD1)
    • At least 4 weeks from last dose of prior other biologic agents
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (Karnofsky > 70%)
  • Absolute lymphocytes > 500/mcL
  • Absolute neutrophil count > 1,000/mcL
  • Platelets > 100,000/mcL
  • Total bilirubin within normal institutional limits
  • Prothrombin time (PT)/partial thromboplastin time (PTT) < 1.5 x upper limit of normal (ULN)
  • Hemoglobin (Hgb) > 9 g/dL
  • Alkaline phosphatase =< 2.5 x ULN
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2 x institutional upper limit of normal
  • Serum creatinine < 1.5 x ULN or creatinine clearance > 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Thyroid function thyroxine (T4), thyroid stimulating hormone (TSH) within normal limits; pre-existing hypothyroidism is acceptable as long as patient has been stable on thyroid replacement for four months prior to entering the study
  • No known central nervous system (CNS) metastases or neurological symptoms possibly related to active CNS metastasis
  • Females of childbearing potential must have a negative pregnancy test within 48 hours prior to initiation of protocol therapy; note: subjects are considered not of child bearing potential if they are surgically sterile, they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy or they are postmenopausal; menopause is the age associated with complete cessation of menstrual cycles, menses, and implies the loss of reproductive potential; by a practical definition, it assumes menopause after 1 year without menses with an appropriate clinical profile at the appropriate age; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from the time the consent is signed and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; women of child-bearing potential and men treated or enrolled on this protocol must also agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) 4 months after completion of rhIL15
  • Ability to understand and the willingness to sign a written informed consent document
  • No history of any hematopoietic malignancy
  • No active (as defined by requiring immunosuppressive therapy) or history of clinically significant autoimmune disease (as defined by previously requiring immunosuppressive therapy)
  • No evidence of a clinically significant active infection
  • No systemic or inhaled corticosteroids or immunosuppressive therapy within 7 days prior to initiation of protocol therapy; note: use of topical corticosteroids and/or eye drops containing glucocorticosteroids is acceptable
  • No immunosuppressive therapy within 30 days prior to initiation of protocol therapy
  • No history of severe asthma, as defined by prior or current use of systemic corticosteroids for disease control, with the exception of physiological replacement doses of cortisone acetate or equivalent, as defined by a dose of 10mg or less; note: history of mild asthma not requiring daily therapy is eligible
  • No history of pulmonary disease such as emphysema or chronic obstructive pulmonary disease (COPD), (forced expiratory volume in one second [FEV1] > 2L or >= 50% of predicted for height and age); pulmonary function tests (PFTs) are required in patients with significant pulmonary or smoking history
  • No history of human immunodeficiency virus (HIV), active or chronic hepatitis B, hepatitis C or human T-cell lymphotropic virus (HTLV-I) infection; note: a positive hepatitis B serology indicative of previous immunization (i.e., hepatitis B surface antibody [HBsAb] positive and hepatitis B core antibody [HBcAb] negative), or a fully resolved acute hepatitis B virus (HBV) infection is not an exclusion criterion
  • Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal, barrier method of birth control or abstinence) from the time the consent is signed, during the duration of study participation and 4 months after discontinuation of protocol therapy
  • Females must not be breastfeeding
  • No evidence of clinically significant congestive heart failure, (ejection fraction of 45% or greater)
  • No platelet or blood transfusions within two weeks of obtaining baseline laboratory values
  • No blood modifiers while enrolled in the study (i.e., growth factors such as erythropoiesis-stimulating agent [ESA] or filgrastim [G-CSF]); note: blood transfusions are allowed per institutional guidelines

Exclusion Criteria:

  • Patients who have had chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C), or radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Class II or greater congestive heart failure as described in the New York Heart Association Functional Classification criteria
  • Patients with primary brain cancer or known brain metastases should be excluded from this clinical trial
  • Patients who have received prior anti-CTLA4 or anti-PD1 therapy less than 8 weeks prior to enrollment
  • Patients who have received prior biologic agents less than 4 weeks prior to enrollment
  • Patients who have received prior interferon or IL-2 therapy less than 4 weeks prior to enrollment
  • Patients who are receiving any other investigational agents
  • ECOG score greater than 1 (Karnofsky < 70%)
  • Human immunodeficiency virus (HIV)-positive patients
  • Positive hepatitis C serology
  • Inability to home monitor blood pressure
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01727076

Locations
United States, California
Stanford University Hospitals and Clinics Active, not recruiting
Stanford, California, United States, 94305
United States, Maryland
National Institutes of Health Active, not recruiting
Bethesda, Maryland, United States, 20892
United States, Minnesota
University of Minnesota Medical Center-Fairview Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Jeffrey S. Miller    612-624-2620      
Principal Investigator: Jeffrey S. Miller         
United States, Washington
Seattle Cancer Care Alliance Recruiting
Seattle, Washington, United States, 98109
Contact: John A. Thompson    800-804-8824      
Principal Investigator: John A. Thompson         
United States, Wisconsin
University of Wisconsin Hospital and Clinics Recruiting
Madison, Wisconsin, United States, 53792
Contact: Douglas G. McNeel    877-405-6866      
Principal Investigator: Douglas G. McNeel         
Sponsors and Collaborators
Investigators
Principal Investigator: Jeffrey Miller Cancer Immunotherapy Trials Network
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01727076     History of Changes
Other Study ID Numbers: NCI-2012-02205, NCI-2012-02205, CITN11-02, CITN11-02, U01CA154967
Study First Received: November 12, 2012
Last Updated: July 11, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Nose Neoplasms
Carcinoma
Carcinoma, Non-Small-Cell Lung
Carcinoma, Renal Cell
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Laryngeal Diseases
Lung Neoplasms
Melanoma
Tongue Neoplasms
Carcinoma, Verrucous
Neoplasms, Unknown Primary
Salivary Gland Neoplasms
Laryngeal Neoplasms
Paranasal Sinus Neoplasms
Oropharyngeal Neoplasms
Nasopharyngeal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms

ClinicalTrials.gov processed this record on August 26, 2014