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

A Phase II Study of Interleukin-21 (IL-21) in Patients With Metastatic or Recurrent Malignant Melanoma

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.

Study Overview

• Status: Completed
• Conditions: Melanoma (Skin)
• Intervention / Treatment: Biological: recombinant human interleukin-21; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis; Other: pharmacological study

Detailed Description

OBJECTIVES:

Primary

• 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.

Secondary

• 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
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • British Columbia
    • Surrey, British Columbia, Canada, V3V 1Z2
      • BCCA - Fraser Valley Cancer Centre
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BCCA - Vancouver Cancer Centre
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Centre at Hamilton Health Sciences
    • Toronto, Ontario, Canada, M4N 3M5
      • Odette Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H2L 4M1
      • CHUM - Hopital Notre-Dame

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS:

• 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

PRIOR CONCURRENT THERAPY:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Recombinant human interleukin-21

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Objective tumor response as assessed by RECIST	after completion of treatment
Overall response rate (complete and partial)	after completion of study
Stable disease rate	after completion of study
Progressive disease rate	after completion of study
Median time to progression	after completion of study
Response duration (median and range)	after completion of study

Collaborators and Investigators

• Sponsor: NCIC Clinical Trials Group
• Collaborators: ZymoGenetics
• Investigators: Study Chair: Teresa M. Petrella, Toronto Sunnybrook Regional Cancer Centre

Publications and helpful links

General Publications

• Petrella TM, Tozer R, Belanger K, Savage KJ, Wong R, Smylie M, Kamel-Reid S, Tron V, Chen BE, Hunder NN, Hagerman L, Walsh W, Eisenhauer EA. Interleukin-21 has activity in patients with metastatic melanoma: a phase II study. J Clin Oncol. 2012 Sep 20;30(27):3396-401. doi: 10.1200/JCO.2011.40.0655. Epub 2012 Aug 20.

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2007
• Primary Completion (Actual): September 2, 2010
• Study Completion (Actual): July 4, 2012

Study Registration Dates

• First Submitted: August 8, 2007
• First Submitted That Met QC Criteria: August 8, 2007
• First Posted (Estimated): August 9, 2007

Study Record Updates

• Last Update Posted (Actual): August 4, 2023
• Last Update Submitted That Met QC Criteria: August 3, 2023
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: recurrent melanoma; stage IV melanoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: I189; CAN-NCIC-IND189 (Registry Identifier: NCI US - Physician Data Query); IND.189 (Other Identifier: NCIC CTG Trial Identifier); ZYMOGENETICS-CAN-NCIC-IND189 (Other Identifier: Zymogenetics); CDR0000560973 (Other Identifier: PDQ)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO