Phase I Dose Escalation Trial of the Raf Kinase Inhibitor BAY 43-9006 (NSC #724772) as Single Agent for Adults With Relapsed and Refractory Acute Leukemias and Chronic Myeloid Leukemia in Blast Crisis
I. To determine the dose-limiting toxicity(s) (DLTs) and maximally tolerated dose (MTD) of
BAY 43-9006 given orally.
I. To obtain preliminary evidence of tumor response to BAY 43-9006 in patients. II. To
assess the pharmacokinetic profile of BAY 43-9006. III. To characterize the preliminary
profile of adverse events and changes in laboratory parameters in patients treated with BAY
IV. To assess effects of BAY 43-9006 on various cellular properties of leukemic blasts
exposed to drug in vivo and in vitro.
OUTLINE: This is an open-label, dose-escalation study.
Patients receive oral sorafenib twice daily on days 1-14 or 1-21. Treatment repeats every 28
days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Patients achieving a complete remission (CR) may be considered for retreatment with
sorafenib for up to an additional 6 courses upon disease recurrence provided the duration of
CR is longer than 1 month.
Cohorts of 3-6 patients receive escalating doses of sorafenib until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that which 2 of 3 or 2 of
6 patients experience dose-limiting toxicity. A total of 12 patients are treated at the MTD.
After completion of study treatment, patients are followed monthly for up to 1 year.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
DLT defined as non-hematologic > grade 3 or hematologic grade 4 marrow aplasia > 28 days (without leukemia clearance) as assessed by NCI-CTC version 3.0
Observed toxicities will be reported and summarized s with frequencies, type and grade in a descriptive manner. No formal statistical inference will be made on this dose-finding study.
Johns Hopkins University
United States: Food and Drug Administration
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