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

NCT ID: NCT00514085

Last Updated: 2023-08-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-12-13
• Study Completion Date: 2012-07-04

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.

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)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Recombinant human interleukin-21

Group Type: EXPERIMENTAL

recombinant human interleukin-21

Intervention Type: BIOLOGICAL

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 method

Intervention Type: OTHER

Cycle 1 Day 1 and Cycle 1 Day 29

laboratory biomarker analysis

Intervention Type: OTHER

slides will be blocked for 15 minutes in 20% normal goat serum and then incubated in primary antibody

pharmacological study

Intervention Type: OTHER

Starting dose of 50μg/kg/day as an IV push

Interventions

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

Intervention Type: BIOLOGICAL

immunohistochemistry staining method

Cycle 1 Day 1 and Cycle 1 Day 29

Intervention Type: OTHER

laboratory biomarker analysis

slides will be blocked for 15 minutes in 20% normal goat serum and then incubated in primary antibody

Intervention Type: OTHER

pharmacological study

Starting dose of 50μg/kg/day as an IV push

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ZymoGenetics

INDUSTRY

Sponsor Role: collaborator

NCIC Clinical Trials Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Teresa M. Petrella

Role: STUDY_CHAIR

Toronto Sunnybrook Regional Cancer Centre

Locations

Cross Cancer Institute

Edmonton, Alberta, Canada

BCCA - Fraser Valley Cancer Centre

Surrey, British Columbia, Canada

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, Canada

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, Canada

Odette Cancer Centre

Toronto, Ontario, Canada

CHUM - Hopital Notre-Dame

Montreal, Quebec, Canada

Countries

Canada

References

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.

Reference Type: RESULT

PMID: 22915661 (View on PubMed)

Other Identifiers

CAN-NCIC-IND189

Identifier Type: REGISTRY

Identifier Source: secondary_id

IND.189

Identifier Type: OTHER

Identifier Source: secondary_id

ZYMOGENETICS-CAN-NCIC-IND189

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000560973

Identifier Type: OTHER

Identifier Source: secondary_id

I189

Identifier Type: -

Identifier Source: org_study_id