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

NCIC Clinical Trials Group

Status and phase

Completed

Phase 2

Conditions

Melanoma (Skin)

Treatments

Other: pharmacological study

Other: laboratory biomarker analysis

Other: immunohistochemistry staining method

Biological: recombinant human interleukin-21

Study type

Interventional

Funder types

NETWORK

Industry

Identifiers

NCT00514085

CAN-NCIC-IND189 (Registry Identifier)

I189

CDR0000560973 (Other Identifier)

IND.189 (Other Identifier)

ZYMOGENETICS-CAN-NCIC-IND189 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

40 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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