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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01307618
First received: March 1, 2011
Last updated: July 28, 2014
Last verified: March 2014
  Purpose

This randomized phase II trial is studying how well giving vaccine therapy together with or without interleukin-12 followed by daclizumab works in treating patients with metastatic melanoma. Vaccines made from peptides or antigens may help the body build an effective immune response to kill tumor cells. 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, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether vaccine therapy is more effective with interleukin-12 and daclizumab in treating melanoma.


Condition Intervention Phase
Recurrent Melanoma
Stage IV Melanoma
Biological: NA17.A2 peptide vaccine
Biological: recombinant MAGE-3.1 antigen
Biological: recombinant interleukin-12
Biological: MART-1 antigen
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Frequency of vaccine-induced CD8+ T cells assessed by ELISPOT [ Time Frame: Baseline and every 9 weeks (after every 3 vaccinations) ] [ Designated as safety issue: No ]
  • Frequency and absolute number of CD4+CD25+FoxP3+ regulatory T cells from peripheral blood [ Time Frame: Baseline and every 9 weeks (after every 3 vaccinations) ] [ Designated as safety issue: No ]
  • Type and grade of toxicity incidents assessed by Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0) [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Progression-free survival assessed by modified WHO criteria [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Overall survival assessed by modified WHO criteria [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 36
Study Start Date: February 2011
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive 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.
Biological: NA17.A2 peptide vaccine
Given subcutaneously (SC) or intradermically (ID)
Other Name: NA17.A2
Biological: recombinant MAGE-3.1 antigen
Given subcutaneously (SC) or intradermically (ID)
Other Names:
  • MAGE-3
  • MAGE-3.1
  • MAGEA3
Biological: MART-1 antigen
Given SC or ID
Other Names:
  • Antigen LB39-AA
  • Antigen SK29-AA
  • MART-1
  • MART-1 Tumor Antigen
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm II
Patients receive vaccination as in arm I with an admixture of recombinant interleukin-12 (IL-12) ID or SC on days 1, 22, and 50.
Biological: NA17.A2 peptide vaccine
Given subcutaneously (SC) or intradermically (ID)
Other Name: NA17.A2
Biological: recombinant MAGE-3.1 antigen
Given subcutaneously (SC) or intradermically (ID)
Other Names:
  • MAGE-3
  • MAGE-3.1
  • MAGEA3
Biological: recombinant interleukin-12
Given SC or ID
Other Names:
  • cytotoxic lymphocyte maturation factor
  • IL-12
  • interleukin-12
  • natural killer cell stimulatory factor
  • Ro 24-7472
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine whether admixture of recombinant interleukin-12 (IL-12) with vaccine emulsion will increase the frequency of vaccine-induced CD8+ T cells in the blood.

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

III. To determine whether vaccination with or without daclizumab will be safe in this patient population.

SECONDARY OBJECTIVES:

I. To determine whether vaccination with or without daclizumab will have clinical activity in patients with advanced melanoma.

II. To determine whether 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.

Peripheral blood mononuclear cells are collected at baseline and periodically during study for correlative studies.

After completion of study therapy, patients are followed up every 3 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically confirmed melanoma with evidence of metastatic disease 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 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
  • HLA-A2 positive by flow cytometry or standard HLA typing
  • Must agree to undergo biopsy of accessible tumor before and after therapy, when feasible

    • If a biopsy cannot be done, then a prior pathologic specimen from the patient must show tumor cells that are positive for HMB45 and MelanA
    • The tumor must express at least 2 antigens in the vaccine for the patient to be eligible
  • No untreated brain metastases

    • 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 are eligible
  • Life expectancy ≥ 12 weeks
  • ECOG performance status (PS) 0-1 (Karnofsky PS 80-100%)
  • WBC ≥ 3,000/mm³
  • ANC ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 9 g/dL
  • Creatinine ≤ 1.5 times upper limit of normal (ULN)
  • Total bilirubin ≤ 1.5 times ULN
  • AST and ALT ≤ 2 times ULN
  • LDH < 1.25 times ULN
  • 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
  • Negative pregnancy test
  • Not pregnant or nursing
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition of recombinant interleukin-12 (IL-12) or other agents used in the study
  • No 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
  • No patients with intrinsic immunosuppression, including seropositivity for HIV antibody

    • Patients should be tested for HIV infection
  • No 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
  • No 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 positive can be eligible provided they are PCR-negative
  • No active or history of autoimmune disease including, but not limited to, rheumatoid arthritis (RF-positive with current or recent flare), inflammatory bowel disease, systemic lupus erythematosus (clinical evidence with ANA 1:80 or greater), ankylosing spondylitis, scleroderma, multiple sclerosis, autoimmune hemolytic anemia, or immune thrombocytopenic purpura

    • Seropositivity alone will not be considered active autoimmunity
    • Patients with immune-mediated hypothyroidism and/or vitiligo are allowed
  • No active gastrointestinal bleeding or uncontrolled peptic ulcer disease
  • Any number of prior therapies allowed
  • At least 4 weeks since prior chemotherapy or radiotherapy (6 weeks for carmustine or mitomycin C) and recovered
  • No prior vaccine containing any of the melanoma antigen peptides or prior daclizumab
  • No other concurrent investigational agents
  • No concurrent systemic corticosteroids (except physiologic replacement doses), or other immunosuppressive drugs (e.g., cyclosporin A)
  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: NCT01307618

Locations
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Thomas F. Gajewski    773-702-4601    tgajewsk@medicine.bsd.uchicago.edu   
Principal Investigator: Thomas F. Gajewski         
Sponsors and Collaborators
Investigators
Principal Investigator: Thomas Gajewski University of Chicago
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01307618     History of Changes
Other Study ID Numbers: NCI-2011-02580, NCI-2011-02580, UCCRC-10-324-B, CDR0000696233, 10-324-B, 8445, P30CA014599, N01CM00071
Study First Received: March 1, 2011
Last Updated: July 28, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Interleukin-12
Daclizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Adjuvants, Immunologic
Immunologic Factors
Immunosuppressive Agents

ClinicalTrials.gov processed this record on July 28, 2014