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Head and Neck Squamous Cell CarcinomaPhase 1NCT01727076

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

A Phase 1 study testing Laboratory Biomarker Analysis, Pharmacological Study and Recombinant Human Interleukin-15 in people with Head and Neck Squamous Cell Carcinoma and Recurrent Head and Neck Carcinoma, run by National Cancer Institute (NCI) at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 19 years and older
What is being tested?
Laboratory Biomarker Analysis, Pharmacological Study and Recombinant Human Interleukin-15
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
5 sitesUnited States
Study dates
15 Feb 2013to 30 Jun 2016
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 19 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 chemotherapy, biologic, immunologic or targeted therapy
  • At least 4 weeks from last dose of prior chemotherapy with resolution of the acute toxic effects of the therapy
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  • 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 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
  • 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 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 10 mg 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

Who cannot join

  • 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 thyroid disease should be excluded unless their T4 is normal or they are on replacement therapy
  • 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
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  • Patients who have received prior interferon or IL-2 therapy less than 4 weeks prior to enrollment
  • ECOG score greater than 1 (Karnofsky < 70%)
  • HIV-positive patients
  • Positive hepatitis C serology
  • Patients who are receiving any other investigational agents
  • 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

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • University of Minnesota/Masonic Cancer Center

    Minneapolis, Minnesota, 55455

  • Stanford Cancer Institute Palo Alto

    Palo Alto, California, 94304

  • Seattle Cancer Care Alliance

    Seattle, Washington, 98109

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum tolerated dose (MTD) of recombinant human IL15 (rhIL15) administered subcutaneously.

SECONDARY OBJECTIVES:

  1. 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.

Being tested
Laboratory Biomarker Analysis, Pharmacological Study, Recombinant Human Interleukin-15
Medical subject headings
Squamous Cell Carcinoma of Head and Neck, Carcinoma, Non-Small-Cell Lung, Carcinoma, Renal Cell, Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

  • Recombinant Human Interleukin-15Biological

    Also called IL15, Interleukin 15, rhIL-15, rIL15

    Given SC

Study groups in NCT01727076
Study groupRoleWhat they receive
Treatment (recombinant interleukin-15)ExperimentalPatients 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.
Receives: Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Biological: Recombinant Human Interleukin-15

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 28 days

Secondary outcomes (9)

  1. 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).

    Measured: Up to 6 months

  2. 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.

    Measured: Baseline to day 15

  3. 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.

    Measured: Baseline to day 4 of week 2

  4. 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.

    Measured: Baseline to day 4 of week 2

  5. 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.

    Measured: Baseline to day 4 of week 2

  6. 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.

    Measured: Baseline to day 15

  7. 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.

    Measured: Up to day 56 (after 2 courses)

  8. 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.

    Measured: Pre-dose, and 10 minutes, 1, 4, and 24 hours after administration

  9. 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).

    Measured: Up to 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Nov 2012 (estimated)
  2. Study start15 Feb 2013
  3. Primary completion30 Jun 2016
  4. Study completion30 Jun 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01727076
Sponsor's protocol ID
NCI-2012-02205
Other IDs
NCI-2012-02205, CITN11-02, CITN11-02, CITN11-02, U01CA154967
Status last verified
Sep 2017
First submitted
12 Nov 2012
Last updated
15 Sep 2017
Results posted
No
Data monitoring committee
No

Publications

  • Margolin K, Morishima C, Velcheti V, Miller JS, Lee SM, Silk AW, Holtan SG, Lacroix AM, Fling SP, Kaiser JC, Egan JO, Jones M, Rhode PR, Rock AD, Cheever MA, Wong HC, Ernstoff MS. Phase I Trial of ALT-803, A Novel Recombinant IL15 Complex, in Patients with Advanced Solid Tumors. Clin Cancer Res. 2018 Nov 15;24(22):5552-5561. doi: 10.1158/1078-0432.CCR-18-0945. Epub 2018 Jul 25.

    PubMed 30045932

  • Miller JS, Morishima C, McNeel DG, Patel MR, Kohrt HEK, Thompson JA, Sondel PM, Wakelee HA, Disis ML, Kaiser JC, Cheever MA, Streicher H, Creekmore SP, Waldmann TA, Conlon KC. A First-in-Human Phase I Study of Subcutaneous Outpatient Recombinant Human IL15 (rhIL15) in Adults with Advanced Solid Tumors. Clin Cancer Res. 2018 Apr 1;24(7):1525-1535. doi: 10.1158/1078-0432.CCR-17-2451. Epub 2017 Dec 4.

    PubMed 29203590

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Laboratory Biomarker Analysis, Pharmacological Study and Recombinant Human Interleukin-15 in people with Head and Neck Squamous Cell Carcinoma and Recurrent Head and Neck Carcinoma, run by National Cancer Institute (NCI) at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 38 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01727076, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2017.

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