Monoclonal Antibody Therapy and Interleukin-2 in Treating Patients With Metastatic Melanoma

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00058279

Collaborator

(none)

Location

Duration (Months)

Study Details

Study Description

Brief Summary

RATIONALE: Biological therapies, such as MDX-010, work in different ways to stimulate the immune system and stop tumor cells from growing. Interleukin-2 may stimulate a person's white blood cells to kill tumor cells. Combining monoclonal antibody therapy with interleukin-2 may kill more tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of combining monoclonal antibody therapy with interleukin-2 in treating patients who have metastatic melanoma.

Condition or Disease	Intervention/Treatment	Phase
Intraocular Melanoma Melanoma (Skin)	Biological: aldesleukin Biological: ipilimumab	Phase 1/Phase 2

Detailed Description

OBJECTIVES:

Determine the maximum tolerated dose (MTD) of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-CTLA4) in combination with high-dose interleukin-2 (IL-2) in patients with metastatic melanoma. (Phase I is closed to accrual as of 4/13/2004).
Determine the activity of MDX-CTLA4 administered at the MTD with high-dose IL-2 in these patients.
Determine whether the administration of IL-2 alters the pharmacokinetics of MDX-CTLA4 in these patients.
Determine the safety and adverse event profile of this regimen in these patients.

OUTLINE: This is an open-label, dose-escalation study of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-CTLA4).

Phase I: Patients receive MDX-CTLA4 IV on days 0, 21, and 42. Patients also receive high-dose interleukin-2 (IL-2) IV over 15 minutes every 8 hours for up to 15 doses beginning on days 22 and 43. Treatment repeats every 63 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients with an ongoing partial response and no greater than grade 1 toxicity may receive additional courses of therapy. Patients who require discontinuation of MDX-CTLA4 due to toxicity may continue receiving IL-2 at the discretion of the investigator.

Cohorts of 3-6 patients receive escalating doses of MDX-CTLA4 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. (Phase I is closed to accrual as of 4/13/2004).

Phase II: Patients receive treatment as in phase I at the MTD of MDX-CTLA4. Patients who achieve a partial or complete response and later develop recurrent or progressive disease may be retreated at the same dose.

Patients are followed at 3 weeks, every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 3-51 patients (3-18 for phase I and 19-33 for phase II) will be accrued for this study within 1 year. (Phase I is closed to accrual as of 4/13/2004).

Study Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

MDX-CTLA4 Combined With IL-2 for Patients With Metastatic Melanoma

Study Start Date :

Feb 1, 2003

Actual Study Completion Date :

Aug 1, 2006

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed stage IV melanoma
Mucosal or ocular melanoma also eligible
Clinically evaluable disease
At least 1 site of measurable disease

PATIENT CHARACTERISTICS:

Age

16 and over

Performance status

ECOG 0-1

Life expectancy

At least 3 months

Hematopoietic

WBC at least 2,500/mm^3
Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
Hemoglobin at least 10 g/dL
Hematocrit at least 30%

Hepatic

Bilirubin no greater than upper limit of normal (ULN)* (less than 3.0 mg/dL in patients with Gilbert's syndrome)
AST no greater than 3 times ULN*
Hepatitis B surface antigen negative
Hepatitis C antibody nonreactive
No evidence or history of significant hepatic disease that would preclude safe administration of high-dose IL-2 NOTE: *Unless attributable to disease

Renal

Creatinine no greater than 2.0 mg/dL
No evidence or history of significant renal disease that would preclude safe administration of high-dose IL-2

Cardiovascular

No evidence or history of significant cardiac disease that would preclude safe administration of high-dose IL-2
Thallium stress test normal (for patients over 50 years of age or with a history of cardiovascular disease)

Pulmonary

No evidence or history of significant pulmonary disease that would preclude safe administration of high-dose IL-2

Immunologic

HIV negative
No autoimmune disease (including uveitis and autoimmune inflammatory eye disease)
No active infection

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix
No evidence or history of significant gastrointestinal disease that would preclude safe administration of high-dose IL-2
No evidence or history of psychiatric disease that would preclude safe administration of high-dose IL-2
No other underlying medical condition that would make the administration of the study drug hazardous or obscure the interpretation of adverse events
No other concurrent medical condition that would preclude study entry

PRIOR CONCURRENT THERAPY:

Biologic therapy

At least 3 weeks since prior immunotherapy for melanoma and recovered
No prior anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-CTLA4)
No prior high-dose (at least 600,000 IU/kg every 8 hours) interleukin-2 (IL-2)

Chemotherapy