MDX-CTLA4 Combined With IL-2 for Patients With Metastatic Melanoma
- 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
- Determine the activity of MDX-CTLA4 administered at the MTD with high-dose IL-2 in
- 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
- 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).
Masking: Open Label, Primary Purpose: Treatment
Steven A. Rosenberg, MD, PhD
NCI - Surgery Branch
United States: Federal Government
|Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support||Bethesda, Maryland 20892-1182|