Interleukin-2 and Sargramostim After Chemotherapy in Treating Patients With Stage III or Stage IV Melanoma

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase: Withdrawn; Phase 2

Conditions: Melanoma (Skin)

Treatments: Biological: aldesleukin; Procedure: adjuvant therapy; Biological: sargramostim

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00085579

MSKCC-04027

04-027

Details and patient eligibility

About

RATIONALE: Interleukin-2 and sargramostim may stimulate a person's white blood cells to kill melanoma cells.

PURPOSE: This phase II trial is studying how well giving interleukin-2 together with sargramostim works in treating patients with stage III or stage IV melanoma that was previously treated with chemotherapy.

Full description

OBJECTIVES:

Primary

• Determine the frequency of complete response in patients with stage III or IV melanoma who have achieved either a partial response or stable disease after prior systemic chemotherapy and are treated with maintenance biotherapy comprising interleukin-2 and sargramostim (GM-CSF).

Secondary

• Determine the time to progression in patients treated with this regimen.
• Determine the effects of this regimen on lymphocyte subsets in these patients.

OUTLINE: Patients are stratified according to response to prior systemic chemotherapy (stable disease [SD] vs partial response [PR]).

Patients receive sargramostim (GM-CSF) subcutaneously (SC) on days 1-14 and low-dose interleukin-2 (IL-2) SC on days 1-5, 8-12, 15-19, and 22-26. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients also receive pulses of high-dose IL-2* IV continuously over 42 hours on days 1 and 2 of courses 2, 3, 5, 6, 8, 10 and 12.

NOTE: *Low-dose IL-2 and GM-CSF are not administered on days 1 and 2 of high-dose IL-2 administration

Patients who continue to have SD or a PR after 12 courses of therapy may continue to receive treatment with GM-CSF and low-dose IL-2 as described above and high-dose IL-2 on days 1 and 2 of every third course.

PROJECTED ACCRUAL: A total of 20-58 patients (10-29 per stratum) will be accrued for this study.

Sex: All

Ages: 16+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed melanoma

  • Stage III or IV disease
  • No primary ocular melanoma

• Stable disease (SD) or partial response (PR) after prior systemic chemotherapy completed at least 4 weeks ago

  • Patients whose second post-chemotherapy evaluation (performed at least 4 weeks after the first evaluation that demonstrated SD or PR AND within 2 weeks before study entry) of disease demonstrates continued tumor shrinkage are not eligible

  • Patients whose second evaluation shows disease progression are eligible unless one of the following is true:

    • Lactic dehydrogenase (LDH) ≥ 2 times upper limit of normal (ULN)
    • LDH > ULN AND is higher than the patient's highest value before systemic chemotherapy
    • Patient has developed a new tumor measuring > 1 cm in diameter
    • Sum of the longest diameters of the existing tumor has increased > 20%

• Evaluable or measurable disease

• Not potentially curable by surgery

• No active CNS metastases

  • Solitary brain metastasis allowed if completely resected or completely ablated with radiosurgery more than 1 month before study entry

PATIENT CHARACTERISTICS:

Age

• 16 and over

Performance status

• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• WBC ≥ 3,000/mm^3
• Platelet count ≥ 100,000/mm^3
• No active bleeding

Hepatic

• See Disease Characteristics
• Bilirubin ≤ 2.0 mg/dL

Renal

• Creatinine ≤ 1.2 mg/dL

Cardiovascular

• Patients ≥ 50 years of age OR those with one or more cardiac risk factors must demonstrate one of the following:

  • Normal exercise stress test
  • Normal stress thallium test
  • Normal comparable cardiac ischemia evaluation

• LVEF ≥ 40%

Other

• No active infection requiring treatment
• No concurrent medical or psychiatric condition that would increase the potential toxicity of study treatment
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No other concurrent antineoplastic biologic response modifier therapy
• No concurrent antineoplastic vaccine therapy

Chemotherapy

• See Disease Characteristics
• No concurrent antineoplastic chemotherapy

Endocrine therapy

• No concurrent steroidal antiemetics
• No concurrent systemic corticosteroids

Radiotherapy

• See Disease Characteristics
• No concurrent antineoplastic radiotherapy

Surgery

• See Disease Characteristics
• Recovered from prior surgery
• Surgery within the past 4 weeks allowed provided there is no evidence of disease progression

Other

• More than 4 weeks since prior therapy for melanoma
• No other concurrent antineoplastic experimental therapy