The goal of this clinical research study is to find the highest safe doses of PTK 787 (vatalanib) and Gleevec (imatinib mesylate) that can be given to treat Chronic Myelogenous Leukemia-Blastic Phase (CML-BP), Refractory Acute Myelogenous Leukemia (AML), or Agnogenic Myeloid Metaplasia (AMM). Another goal is to see how effective this combination treatment is.
Rationale: The purpose of this study is to combine PTK-787, a potent orally vascular endothelial growth factor (VEGF) receptor inhibitor (in disorders where VEGF is known to be involved in the pathophysiology), with Imatinib mesylate (IM), a protein-tyrosine kinase inhibitor of abl, Bcr-Abl, platelet derived growth factor (PDGF), and c-Kit (in same disorders where these kinases are believed to be important). The potential synergy between oral agents that inhibit these kinases in disorders where each of the two agents have some, but inadequate, single agent activity is being studied in this protocol. We will also have an opportunity to assess if there is any correlation between response and individual kinase mutations e.g., c-Kit in patients with AML. If improved outcomes are observed, further studies will be indicated to investigate which, if either, agent is predominantly responsible for such a benefit - these studies will be facilitated by the availability of more potent e.g., (AMN107 as an abl inhibitor), (Bevacizumab, AG013736 as VEGF inhibitors) agents which will help to define the relative importance of the various inhibitory activities. Objectives: To determine the maximum tolerated doses (MTD) and pharmacokinetics (PK) of PTK 787 and imatinib mesylate, when given in combination to patients with refractory acute myelogenous leukemia (AML), agnogenic myeloid metaplasia (AMM) and chronic myelogenous leukemia in blastic phase (CML-BP). To determine the efficacy (response rate, survival, time to progression, time to treatment failure, duration of response) of the MTD in these study populations.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
9
600 mg by mouth every day (for AML, CML-BP) for a 28 day cycle. 400 mg by mouth every day (for AMM) for a 28 day cycle.
For 1 week prior to receipt of the study combination regimen, all patients will receive single agent PTK 787 at the dose specified for that dose level of the study combination regimen to allow stabilization of PTK 787 levels. Starting dose: 250 mg by mouth every day for a 28 day cycle.
M.D. Anderson Cancer Center
Houston, Texas, United States
Time to Response
Time to response is defined as the period of time from the date of first study drug administration until the first objective documentation of response.
Time frame: 28 days
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