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Recurrent MelanomaPhase 2NCT01307618

Vaccine Therapy With or Without Recombinant Interleukin-12 Followed by Daclizumab in Treating Patients With Metastatic Melanoma

A Phase 2 study testing NA17.A2 Peptide Vaccine, Recombinant MAGE-3.1 Antigen and Recombinant Interleukin-12 in people with Recurrent Melanoma and Stage IV Skin Melanoma, run by National Cancer Institute (NCI) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This randomized phase II trial is studying how well giving vaccine therapy together with or without recombinant interleukin-12 followed by daclizumab works in treating patients with melanoma that has spread to other places in the body. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Recurrent Melanoma, Stage IV Skin Melanoma
What is being tested?
NA17.A2 Peptide Vaccine, Recombinant MAGE-3.1 Antigen and Recombinant Interleukin-12
Type of treatment
Vaccines
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
1 siteUnited States
Study dates
Feb 2011to Feb 2015
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

Who may be able to join

  • Patients must have histologically confirmed melanoma with evidence of metastatic disease either by radiologic or physical examination
  • In-transit metastases are allowed
  • Biopsy should be performed to reconfirm the diagnosis in cases of doubt
  • Patients must have measurable disease
  • For computed tomography (CT) imaging, this is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm by conventional techniques or as ≥ 10 mm by spiral CT scan
  • For cutaneous lesions, these must be measurable with a ruler and documented photographically with a ruler in place
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  • There are no limits on the number of prior therapies; patients must not have received a vaccine containing any of the melanoma antigen peptides, nor previously received daclizumab; at least 4 weeks must have passed since prior chemotherapy or radiation therapy (6 weeks for BCNU [carmustine] or mitomycin C)
  • Life expectancy greater than or equal to 12 weeks
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Karnofsky ≥ 80%)
  • Leukocytes ≥ 3,000/mcL
  • Absolute neutrophil count (ANC) ≥ 1,500/mcL
  • Hemoglobin ≥ 9 g/dL
  • Platelets ≥ 100,000/mcL
  • Creatinine ≤ 1.5 x upper limit of normal (ULN)
  • Total bilirubin ≤ 1.5 x ULN
  • Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) ≤ 2 x institutional ULN
  • Lactate dehydrogenase (LDH) < 1.25 x ULN
  • Human leukocyte antigen (HLA) typing: patient must express HLA-A2, either by flow cytometry or by standard HLA typing
  • Patient must agree to undergo biopsy of accessible tumor before and after therapy, when feasible, to study tumor cell properties and characteristics of immune cells; if a biopsy cannot be done, then a prior pathologic specimen from the patient must show tumor cells that are positive for melanosome specific antigen (HMB45) and MLANA (MelanA); the tumor must express at least 2 antigens in the vaccine for the patient to be eligible
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal, barrier method of birth control, or abstinence) prior to study entry, for the duration of treatment, and for 2 months after completion of treatment; a pregnancy test must be done and be negative for women of child-bearing potential; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • Patients who have had chemotherapy, biological or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Patients may not be receiving any other investigational agents
  • Presence of untreated brain metastases; all patients must undergo brain imaging as part of the pre-study evaluation; only patients with no brain metastases, or with brain lesions successfully treated by stereotactic radiation or surgical removal without progression at 28-day follow-up and off corticosteroids for 4 weeks, will be eligible
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition IL-12 or other agents used in the study
  • Concurrent systemic corticosteroids (except physiologic replacement doses) or other immunosuppressive drugs (eg. cyclosporin A)
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
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  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with IL-12; women of child-bearing age must be tested for urinary or serum beta-human chorionic gonadotropin (HCG)
  • Patients with intrinsic immunosuppression, including seropositivity for human immunodeficiency virus (HIV) antibody; patients should be tested for HIV; HIV-positive patients are ineligible
  • Psychiatric illness that may make compliance to the clinical protocol unmanageable or may compromise the ability of the patient to give informed consent; patients with clinical evidence of dementia should have a competent designee participate in decision making
  • Serious concurrent infection, including active tuberculosis, hepatitis B, or hepatitis C; patients should be tested for hepatitis B surface antigen and hepatitis C antibody; patients who are hepatitis C antibody (Ab) positive can be eligible if they are polymerase chain reaction (PCR)-negative
  • Active or history of autoimmune disease including but not limited to: rheumatoid arthritis (rheumatoid factor [RF]-positive with current or recent flare), inflammatory bowel disease, systemic lupus erythematosis (clinical evidence with antinuclear antibody [ANA] 1:80 or greater), ankylosing spondylitis, scleroderma, multiple sclerosis, autoimmune hemolytic anemia, and immune thrombocytopenic purpura; seropositivity alone will not be considered active autoimmunity; patients with immune-mediated hypothyrodisim and/or vitiligo are allowed
  • Active gastrointestinal bleeding or uncontrolled peptic ulcer disease

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

Other trials in United States

About this study

Official title: A Randomized Phase II Study of Multipeptide Vaccination With or Without IL-12, Then Combined With Regulatory T Cell Depletion Using Daclizumab in Patients With Metastatic Melanoma

This randomized phase II trial is studying how well giving vaccine therapy together with or without recombinant interleukin-12 followed by daclizumab works in treating patients with melanoma that has spread to other places in the body. Vaccines made from peptides or antigens may help the body build an effective immune response to kill tumor cells. Recombinant interleukin-12 may kill tumor cells by stopping blood flow to the tumor and by stimulating white blood cells to kill melanoma cells. Monoclonal antibodies, such as daclizumab, may decrease the number of regulatory T cells (T cells that suppress the activation of the immmune system) and may lead to a better immune response against melanoma. It is not yet known whether vaccine therapy is more effective with interleukin-12 and daclizumab in treating melanoma.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine if admixture of IL-12 (recombinant interleukin-12) with vaccine emulsion will increase the frequency of vaccine-induced cluster of differentiation (CD)8+ T cells in the blood.

II. To determine if administration of daclizumab will deplete CD4+CD25+ regulatory T cells from the peripheral and potentiate specific immune responses induced by vaccination.

III. To determine if vaccination +/- daclizumab will be safe in this patient population.

SECONDARY OBJECTIVES:

  1. To determine if vaccination +/- daclizumab will have clinical activity in patients with advanced melanoma.

II. To determine if clinical response may be associated with particular gene expression profiles in the tumor microenvironment.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive multipeptide vaccination comprising recombinant MAGE-3.1 antigen, MART-1 antigen, gp100 antigen, and NA17-A2 peptide emulsified with Montanide ISA-51 intradermically (ID) or subcutaneously (SC) on days 1, 22, and 50.

ARM II: Patients receive vaccination as in arm I with an admixture of recombinant interleukin-12 (IL-12) on days 1, 22, and 50.

In both arms, patients are evaluated for immune response. Patients with partial response or stable disease may be immunized for up to a maximum of 1 year. Patients with complete response may be treated with 1 additional course of 3 vaccinations.

EXPANDED COHORT: Additional patients are accrued to the arm with higher immune response and receive daclizumab IV over 15 minutes on day -7. Patients then receive vaccination as in arm I or arm II on days 1, 22, and 50 in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up every 8 weeks until disease progression and then at least every 3 months thereafter.

Being tested
NA17.A2 Peptide Vaccine, Recombinant MAGE-3.1 Antigen, Recombinant Interleukin-12, MART-1 Antigen, Laboratory Biomarker Analysis
Medical subject headings
Melanoma

What participants receive

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

  • NA17.A2 Peptide VaccineBiological

    Also called NA17.A2

    Given SC or ID

  • Recombinant MAGE-3.1 AntigenBiological

    Also called MAGE-3, MAGE-3.1

    Given SC or ID

  • Recombinant Interleukin-12Biological

    Given SC or ID

  • MART-1 AntigenBiological

    Also called Antigen LB39-AA, Antigen SK29-AA, MART-1 Tumor Antigen

    Given SC or ID

  • Laboratory Biomarker AnalysisOther

    Correlative studies

Study groups in NCT01307618
Study groupRoleWhat they receive
Arm I (vaccine therapy)ExperimentalPatients receive vaccination comprising recombinant MAGE-3.1 antigen, MART-1 antigen, gp100 antigen, and NA17-A2 peptide emulsified with Montanide ISA-51 ID or SC on days 1, 22, and 50.
Receives: Biological: NA17.A2 Peptide Vaccine; Biological: Recombinant MAGE-3.1 Antigen; Biological: MART-1 Antigen; Other: Laboratory Biomarker Analysis
Arm II (vaccine therapy, IL-12)ExperimentalPatients receive vaccination as in arm I with an admixture of IL-12 ID or SC on days 1, 22, and 50.
Receives: Biological: NA17.A2 Peptide Vaccine; Biological: Recombinant MAGE-3.1 Antigen; Biological: Recombinant Interleukin-12; Other: Laboratory Biomarker Analysis

What is being measured

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

  1. Frequency of Vaccine-induced CD8+ T Cells Assessed by Enzyme-linked Immunospot (ELISPOT)

    Data before treatment and after 3 vaccines will be assessed using paired t-tests within each cohort as well as a two-sample t-test of the mean post-treatment levels between cohorts. Repeated measures analysis of variance or mixed effects models will be utilized to further characterize changes in the levels of circulating T cells over time.

    Measured: Up to 4 years

  2. Absolute Number of CD4+CD25+FoxP3+ Regulatory T Cells From Peripheral Blood

    Descriptive statistics and paired t-tests will be generated to describe the frequency and absolute number of CD4+CD25+FoxP3+ cells before and after daclizumab, and also at subsequent time points. Repeated measures of analysis of variance and mixed effects models will be used to further evaluate change in numbers over time, and to compare these changes between cohorts.

    Measured: Up to 4 years

  3. Type and Grade of Toxicity Incidents Assessed by Common Toxicity Criteria Version 4.0 (CTCAE v4.0)

    Measured: Up to 4 years

Secondary outcomes (3)

  1. Progression-free Survival Assessed by Modified World Health Organization (WHO) Criteria

    Median progression-free survival and the associated 95% confidence limits will be derived using the procedure described in Brookmeyer and Crowley.

    The criteria for progressive disease are 1) appearance of new lesions, 2) 25% increase in the sum of the product of the largest perpendicular diameters of the indicator lesions, or 3) reappearance of any tumor.

    Measured: Up to 4 years

  2. Overall Survival Assessed by Modified WHO Criteria

    Median overall survival and the associated 95% confidence limits will be derived using the procedure described in Brookmeyer and Crowley.

    Measured: Up to 4 years

  3. Gene Expression Profiles

    Gene cluster analysis will be performed using deoxyribonucleic acid (DNA)-Chip Analyzer (dCHIP) software and comparisons will be made before and after treatment in each individual patient, and between responders and non-responders. Attempts will be made to identify gene expression profiles that correlate with clinical outcome.

    Measured: Up to 4 years

Timeline

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

  1. First posted3 Mar 2011 (estimated)
  2. Study startFeb 2011
  3. Primary completionJan 2015
  4. Study completionFeb 2015

Why it stopped: Due to lack of clinical efficacy and lack of drug supply, trial was closed early and correlative studies were not pursued further.

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01307618
Sponsor's protocol ID
NCI-2011-02580
Other IDs
NCI-2011-02580, UCCRC-10-324-B, CDR0000696233, 10-324-B, 8445, P30CA014599, N01CM00071
Status last verified
Aug 2016
First submitted
1 Mar 2011
Last updated
24 Oct 2016

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing NA17.A2 Peptide Vaccine, Recombinant MAGE-3.1 Antigen and Recombinant Interleukin-12 in people with Recurrent Melanoma and Stage IV Skin Melanoma, run by National Cancer Institute (NCI) at 1 site 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 21 inclusion and 12 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: stopped early, as of the sponsor's last update on 24 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Oct 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Frequency of Vaccine-induced CD8+ T Cells Assessed by Enzyme-linked Immunospot (ELISPOT) (time frame: Up to 4 years). The study lists 3 primary outcomes in all. 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 NCT01307618.

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 24 Oct 2016.

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