The purpose of this multi-center, open-label, escalating dose study is to assess the safety and tolerability of PPI-2458 in subjects with Non-Hodgkin's Lymphoma (NHL)and solid tumors. Subjects will be treated every other day (QOD) with PPI-2458 while being monitored closely for adverse events.
The study will first determine the dose level that maximally inhibits MetAP2 in white blood cells (WBC). Once this dose level is reached, the study will proceed into the next cohort (dose level) to investigate the dose level that maximally inhibits MetAP2 in tumor tissue biopsies. Free MetAP2 levels (WBC and/or tumor tissue) will be analyzed during the first cycle (28 days) of treatment. Cohorts are expected to enroll every two cycles until the maximum tolerated dose (MTD)is determined. After the Initial Treatment Phase of two treatment cycles of PPI-2458, subjects may continue into a Continuous Treatment Phase at the discretion of the Investigator. In order to be eligible for the Continuous Treatment Phase of the protocol, subjects must have received some benefit (e.g., stable disease) as assessed by the Investigator within the Initial Treatment Phase and must continue to meet inclusion and exclusion criteria.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
45
Universtiy of Maryland Marlene and Stewart Greenebaum Cancer Center
Baltimore, Maryland, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
Safety will be determined by clinical adverse events, laboratory abnormalities, withdrawals due to adverse events, and drug-related neurotoxicities.
Pharmacokinetic assessment of PPI-2458
Pharmacodynamic assessment of PPI-2458
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Boston, Massachusetts, United States
University of New Mexico
Albuquerque, New Mexico, United States
Columbia University Medical Center
New York, New York, United States
University of Texas, M.D. Anderson Cancer Center
Houston, Texas, United States
Virginia Oncology Associates
Norfolk, Virginia, United States