Melanoma (Skin)Phase 2NCT00514085
Interleukin-21 in Treating Patients With Metastatic or Recurrent Malignant Melanoma
A Phase 2 study testing recombinant human interleukin-21, immunohistochemistry staining method and laboratory biomarker analysis in people with Melanoma (Skin), run by NCIC Clinical Trials Group at 7 sites in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma (Skin)
- What is being tested?
- recombinant human interleukin-21, immunohistochemistry staining method and laboratory biomarker analysis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 7 sitesCanada
- Study dates
- 13 Dec 2007to 4 Jul 2012
- Phase
- Phase 2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
Canada7 sites
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, L8V 5C2
CHUM - Hopital Notre-Dame
Montreal, Quebec, H2L 4M1
BCCA - Fraser Valley Cancer Centre
Surrey, British Columbia, V3V 1Z2
Odette Cancer Centre
Toronto, Ontario, M4N 3M5
BCCA - Vancouver Cancer Centre
Vancouver, British Columbia, V5Z 4E6
CancerCare Manitoba
Winnipeg, Manitoba, R3E 0V9
About this study
Official title: 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.
Read the 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.
- Conditions
- Melanoma (Skin)
- Being tested
- recombinant human interleukin-21, immunohistochemistry staining method, laboratory biomarker analysis, pharmacological study
- Keywords
- recurrent melanoma, stage IV melanoma
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
recombinant human interleukin-21Biological
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
immunohistochemistry staining methodOther
Cycle 1 Day 1 and Cycle 1 Day 29
laboratory biomarker analysisOther
slides will be blocked for 15 minutes in 20% normal goat serum and then incubated in primary antibody
Starting dose of 50μg/kg/day as an IV push
| Study group | Role | What they receive |
|---|---|---|
| Recombinant human interleukin-21 | Experimental | Not described Receives: Biological: recombinant human interleukin-21; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis; Other: pharmacological study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective tumor response as assessed by RECIST
Measured: after completion of treatment
Overall response rate (complete and partial)
Measured: after completion of study
Stable disease rate
Measured: after completion of study
Progressive disease rate
Measured: after completion of study
Median time to progression
Measured: after completion of study
Response duration (median and range)
Measured: after completion of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2007 (estimated)
- Study start13 Dec 2007
- Primary completion2 Sep 2010
- Study completion4 Jul 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Melanoma (Skin)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- NCIC Clinical Trials Group
- Sponsor type
- Research network
- Collaborators
- ZymoGenetics
- Responsible party
- Sponsor
- Investigators
- Teresa M. Petrella, Study chair, Toronto Sunnybrook Regional Cancer Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00514085
- Sponsor's protocol ID
- I189
- Other IDs
- CAN-NCIC-IND189, IND.189, ZYMOGENETICS-CAN-NCIC-IND189, CDR0000560973
- Status last verified
- Apr 2020
- First submitted
- 8 Aug 2007
- Last updated
- 4 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
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.
PubMed 22915661
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Interleukin-21 (IL-21) in Patients With Metastatic or Recurrent Malignant Melanoma
- ClinicalTrials.gov ID
- NCT00514085
- Acronym / sponsor ID
- I189
- Conditions
- Melanoma (Skin)
- Keywords
- recurrent melanoma, stage IV melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- NCIC Clinical Trials GroupResearch network
- Collaborators
- ZymoGenetics
- Study start
- 13 Dec 2007 (actual)
- Primary completion
- 2 Sep 2010 (actual)
- Study completion
- 4 Jul 2012 (actual)
- First posted
- 9 Aug 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Recombinant human interleukin-21 | Experimental | Biological: recombinant human interleukin-21, Other: immunohistochemistry staining method, Other: laboratory biomarker analysis, Other: pharmacological study |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| recombinant human interleukin-21Patients 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 | Biological | Recombinant human interleukin-21 |
| immunohistochemistry staining methodCycle 1 Day 1 and Cycle 1 Day 29 | Other | Recombinant human interleukin-21 |
| laboratory biomarker analysisslides will be blocked for 15 minutes in 20% normal goat serum and then incubated in primary antibody | Other | Recombinant human interleukin-21 |
| pharmacological studyStarting dose of 50μg/kg/day as an IV push | Other | Recombinant human interleukin-21 |
Primary outcome
Objective tumor response as assessed by RECIST
Time frame: after completion of treatment
Overall response rate (complete and partial)
Time frame: after completion of study
Stable disease rate
Time frame: after completion of study
Progressive disease rate
Time frame: after completion of study
Median time to progression
Time frame: after completion of study
Response duration (median and range)
Time frame: after completion of study
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2023.
- Results publication: PubMed 22915661Petrella 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Teresa M. Petrella study chair
Toronto Sunnybrook Regional Cancer Centre
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing recombinant human interleukin-21, immunohistochemistry staining method and laboratory biomarker analysis in people with Melanoma (Skin), run by NCIC Clinical Trials Group at 7 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 4 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Canada. 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?
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?
Objective tumor response as assessed by RECIST (time frame: after completion of treatment). The study lists 6 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 NCT00514085, which also lists 1 linked publication.
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 4 Aug 2023.