A Phase I Study of PS-341 in Patients With Hematologic Malignancies
OBJECTIVES: I. Determine the maximum tolerated dose and dose-limiting toxicity of PS-341 in
patients with hematologic malignancies. II. Determine the pharmacodynamics of this drug in
these patients. III. Determine response to this drug in these patients. IV. Determine the
correlation between response of malignancies and proteasome inhibition and apoptosis in
peripheral blood mononuclear cells (PBMC) of these patients. V. Determine the correlation
between therapy toxicity and proteasome inhibition and apoptosis in PBMC of these patients.
VI. Determine the effect of this drug on other molecular markers (i.e., BCL-2 in follicular
lymphoma patients and t9;22/BCR/ABL in chronic lymphocytic leukemia patients). VII.
Determine the correlation between interleukin-6 serum levels in multiple myeloma patients
and drug dosing, toxicity of therapy, extent of protease inhibition, response to therapy,
and apoptosis in PBMC of these patients.
OUTLINE: This is a dose-escalation, multicenter study. Patients receive PS-341 IV over 30
minutes on days 1, 4, 8, 11, 15, 18, 22, and 25 followed by a 2-week rest. Treatment repeats
every 6 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6
patients receive escalating doses of PS-341 until the maximum tolerated dose (MTD) is
determined. The MTD is defined as the dose at which 2 of 6 patients experience dose-limiting
PROJECTED ACCRUAL: A total of 3-30 patients will be accrued for this study.
Primary Purpose: Treatment
Steven Soignet, MD
Memorial Sloan-Kettering Cancer Center
United States: Federal Government
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|