Interleukin-21 in Treating Patients With Metastatic or Recurrent Malignant Melanoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00514085
Recruitment Status : Completed
First Posted : August 9, 2007
Last Update Posted : November 28, 2016
Information provided by (Responsible Party):
Canadian Cancer Trials Group ( NCIC Clinical Trials Group )

Brief Summary:

RATIONALE: Interleukin-21 may stimulate white blood cells, including natural killer cells, to kill melanoma cells.

PURPOSE: This phase II trial is studying the side effects and how well interleukin-21 works in treating patients with metastatic or recurrent malignant melanoma.

Condition or disease Intervention/treatment Phase
Melanoma (Skin) Biological: recombinant human interleukin-21 Other: immunohistochemistry staining method Other: laboratory biomarker analysis Other: pharmacological study Phase 2

Detailed Description:



  • To assess the efficacy, in terms of objective response rate, nonprogression rate, time to progression, and response duration, in patients with metastatic or recurrent malignant melanoma treated with recombinant human interleukin-21 (rIL-21).
  • To assess the toxicity and safety of rIL-21 in patients with previously untreated metastatic or recurrent malignant melanoma.
  • To characterize the pharmacokinetics of rIL-21.
  • To characterize the effects of rIL-21 on lymphocyte cell count and soluble CD25 (sCD25) in serum as potential biomarkers for drug activity.
  • To evaluate the immunogenicity of rIL-21, specifically preexisting immunogenicity to the drug and antibody induction during treatment.
  • To assess melanoma antigenic markers for response and nonprogression on archival tissue from patients enrolled on the study.


  • To investigate whether rIL-21 induced sCD25 release is independent of the level of circulating sCD25.
  • To investigate the effect of rIL-21 on antibody induction during treatment and preexisting immunogenicity.
  • To assess lymphocyte cell-count changes over time in relation to rIL-21 therapy.

OUTLINE: This is a multicenter study.

Patients receive recombinant human interleukin-21 (rIL-21) IV on days 1-5 of weeks 1, 3 and 5. Treatment repeats every 8 weeks in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) or partial response (PR) receive 2 courses beyond CR or PR. Patients with stable disease receive a maximum of 3 courses of rIL-21.

Previously archived tumor tissue and blood samples are collected from patients for correlative studies. Samples are analyzed for soluble CD25, rIL-21 antibodies, circulating lymphocyte counts, preexisting immonogenicity to rIL-21 for antibody induction, and expression of common melanoma tumor antigen markers via IHC.

After completion of study treatment, patients are followed at 4 weeks.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Interleukin-21 (IL-21) in Patients With Metastatic or Recurrent Malignant Melanoma
Study Start Date : July 2007
Actual Primary Completion Date : September 2010
Actual Study Completion Date : July 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Intervention Details:
  • Biological: recombinant human interleukin-21

    Patients enrolled in Part A will receive treatment daily x 5 on weeks 1, 3, and 5 of an 8 week cycle.

    Patients enrolled in Part B will receive treatment daily x 5 on weeks 1, and 3 of a 6 week cycle

  • Other: immunohistochemistry staining method
    Cycle 1 Day 1 and Cycle 1 Day 29
  • Other: laboratory biomarker analysis
    slides will be blocked for 15 minutes in 20% normal goat serum and then incubated in primary antibody
  • Other: pharmacological study
    Starting dose of 50μg/kg/day as an IV push

Primary Outcome Measures :
  1. Objective tumor response as assessed by RECIST [ Time Frame: after completion of treatment ]
  2. Overall response rate (complete and partial) [ Time Frame: after completion of study ]
  3. Stable disease rate [ Time Frame: after completion of study ]
  4. Progressive disease rate [ Time Frame: after completion of study ]
  5. Median time to progression [ Time Frame: after completion of study ]
  6. Response duration (median and range) [ Time Frame: after completion of study ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed cutaneous malignant melanoma

    • Recurrent or metastatic disease that is not curable by surgical or other means
  • Clinically and/or radiologically documented disease defined as at least one site of disease unidimensionally measurable ≥ 20 mm by x-ray, physical exam, or nonspiral CT scan OR ≥ 10 mm by spiral CT scan
  • Must have nonbulky metastatic disease defined as the largest measurable lesion ≤ 50 mm in maximum diameter
  • Must have primary diagnosis tumor tissue or previously resected metastatic melanoma tissue available (i.e., paraffin block or unstained slides)
  • No known brain metastases


  • ECOG performance status 0-2
  • Life expectancy ≥ 12 weeks
  • Absolute granulocytes count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Bilirubin normal
  • Serum creatinine ≤ 1.5 times upper limit of normal (ULN)
  • AST and ALT ≤ 2.5 times ULN
  • Negative pregnancy test
  • Not pregnant or nursing
  • Fertile patients must use effective contraception during study therapy
  • No uncontrolled intercurrent illness or condition including, but not limited to, any of the following:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Psychiatric illness or social situation that would limit compliance with study requirements
  • No history of hemolysis or a hemolytic disorder including, but not limited to, any of the following:

    • Sickle cell anemia
    • Thalassemia
    • Autoimmune hemolytic anemia
  • No history of other malignancies within the past 5 years except adequately treated nonmelanoma skin cancer, curatively treated carcinoma in situ of the cervix, or other solid tumors curatively treated with no evidence of disease
  • No known HIV, hepatitis B, or hepatitis C infection
  • Patients must reside within a 2-hour drive from a participating center


  • No previous systemic therapy for metastatic disease
  • At least 3 months since prior adjuvant immunotherapy for recurrent melanoma

    • No prior immunotherapy for metastatic disease
    • No prior immunotherapy outside the adjuvant setting
  • At least 4 weeks since prior major surgery
  • At least 4 weeks since prior radiotherapy except low-dose, nonmyelosuppressive radiotherapy and recovered
  • More than 4 weeks since prior and no concurrent investigational agents or anticancer therapy
  • No prior chemotherapy including regional therapy
  • No concurrent systemic corticosteroids (e.g., prednisone or dexamethasone)

    • Concurrent topical steroids are allowed

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00514085

Canada, Alberta
Cross Cancer Institute
Edmonton, Alberta, Canada, T6G 1Z2
Canada, British Columbia
BCCA - Fraser Valley Cancer Centre
Surrey, British Columbia, Canada, V3V 1Z2
BCCA - Vancouver Cancer Centre
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Manitoba
CancerCare Manitoba
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, Ontario
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, Canada, L8V 5C2
Odette Cancer Centre
Toronto, Ontario, Canada, M4N 3M5
Canada, Quebec
CHUM - Hopital Notre-Dame
Montreal, Quebec, Canada, H2L 4M1
Sponsors and Collaborators
NCIC Clinical Trials Group
Study Chair: Teresa M. Petrella Toronto Sunnybrook Regional Cancer Centre

Publications of Results:
Responsible Party: NCIC Clinical Trials Group Identifier: NCT00514085     History of Changes
Other Study ID Numbers: I189
CAN-NCIC-IND189 ( Registry Identifier: NCI US - Physician Data Query )
IND.189 ( Other Identifier: NCIC CTG Trial Identifier )
CDR0000560973 ( Other Identifier: PDQ )
First Posted: August 9, 2007    Key Record Dates
Last Update Posted: November 28, 2016
Last Verified: July 2012

Keywords provided by Canadian Cancer Trials Group ( NCIC Clinical Trials Group ):
recurrent melanoma
stage IV melanoma

Additional relevant MeSH terms:
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas