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


Phase 1/Phase 2
16 Years
N/A
Not Enrolling
Both
Intraocular Melanoma, Melanoma (Skin)

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Trial Information

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


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).

Inclusion Criteria


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

- At least 3 weeks since prior chemotherapy for melanoma and recovered

- No concurrent chemotherapy

Endocrine therapy

- At least 3 weeks since prior hormonal therapy for melanoma and recovered

- At least 4 weeks since prior corticosteroids

- No concurrent systemic or topical corticosteroids

Radiotherapy

- At least 3 weeks since prior radiotherapy for melanoma and recovered

Surgery

- Not specified

Other

- No concurrent immunosuppressive agents (e.g., cyclosporine or its analog)

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

Steven A. Rosenberg, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

NCI - Surgery Branch

Authority:

United States: Federal Government

Study ID:

CDR0000287211

NCT ID:

NCT00058279

Start Date:

February 2003

Completion Date:

August 2006

Related Keywords:

  • Intraocular Melanoma
  • Melanoma (Skin)
  • stage IV melanoma
  • extraocular extension melanoma
  • recurrent melanoma
  • iris melanoma
  • ciliary body and choroid melanoma, medium/large size
  • ciliary body and choroid melanoma, small size
  • recurrent intraocular melanoma
  • Melanoma
  • Uveal Neoplasms

Name

Location

Warren Grant Magnuson Clinical Center - NCI Clinical Studies SupportBethesda, Maryland  20892-1182