A Phase I/II Study of Sorafenib (BAY 43-9006) in Combination With Low Dose ARA-C (CYTARABINE) in Elderly Patients With AML or High-Risk MDS
- To determine the recommended dose of sorafenib tosylate and cytarabine when given in
combination to elderly patients with acute myeloid leukemia or high-risk
myelodysplastic syndromes who are not suitable for intensive chemotherapy. (Phase I)
- To determine the safety, tolerability, toxicity profile, and dose-limiting toxicities
in patients treated with this regimen. (Phase I)
- To estimate the efficacy (as measured by complete response rate) in patients treated
with this regimen. (Phase II)
- To describe the toxic effects and overall response rate (complete and partial) in
patients treated with this regimen. (Phase II)
- To evaluate potential correlates of response in translational research studies
including FLT-3 internal tandem duplications and point mutations in blasts. (Phase II)
OUTLINE: This is a multicenter study.
- Phase I: Patients receive oral sorafenib tosylate twice daily on days 2-28 and
cytarabine subcutaneously twice daily on days 1-10 at the dose level assigned at
registration. Doses of both drugs will be escalated and the recommended doses for the
combination will be determined. Treatment repeats every 28 days for up to 6 courses in
the absence of disease progression or unacceptable toxicity. Patients who respond to
treatment will receive 2 cycles after response criteria are met.
- Phase II: Patients receive sorafenib tosylate and cytarabine as in phase I at the
recommended doses for the combination determined in phase I.
Bone marrow (or blood) samples are collected at baseline and at the end of each course of
study treatment. Baseline samples are analyzed for mutational status of FLT-3 (i.e.,
internal tandem duplication [ITD] and point mutations).
After completion of study treatment, patients are followed at 4 weeks and then every 3
months thereafter until progression and toxicities resolve.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Recommended phase II dose of sorafenib tosylate when given in combination with cytarabine (Phase I)
Brian Leber, MD, FRCPC
McMaster Children's Hospital at Hamilton Health Sciences
Canada: Health Canada