Trial of Mitogen-activated Protein/Extracellular Signal-regulated Kinase (MEK) Inhibitor

Inclusion criteria:

Phase 1:

1. Subjects with one of the following conditions:

   • Primary or secondary Acute Myeloid Leukemia, pathologically confirmed according to World Health Organization classification
   • Subjects with myelodysplastic syndrome, International Prognostic Scoring System Int-2 or high risk who are resistant or intolerant to standard treatment and not candidates for transplantation,
   • Subjects with relapsed or refractory multiple myeloma, who have failed or are intolerant to at least two prior therapies including thalidomide, lenalidomide and bortezomib,
   • Subjects with advanced myeloproliferative disorders for whom no established treatment options are available,
   • Subjects with acute lymphocytic leukemia, relapsed, refractory or intolerant to standard treatment and for whom no effective treatment options are available,
2. Age greater than or equal to 18 years.
3. Subjects have read and understood the Informed Consent Form
4. Subjects and their partners must be willing to avoid pregnancy during the trial

Phase 2:

1. Subjects with newly diagnosed primary or secondary Acute Myeloid Leukemia pathologically confirmed according to World Health Organization classification who have NOT been exposed to any prior therapy for Acute Myeloid Leukemia.

2. Subjects meet at least one of the following conditions:

   • Age greater than or equal to 75 years OR

   • Age greater than or equal to 60 and less than 75 years with at least one of the following poor prognostic factors:

     • Secondary Acute Myeloid Leukemia
     • At least one of the following unfavorable cytogenetic abnormalities: del(5q), -5, -7, del(7q), abn 3q, 9q, 11q, 20q, 21q, 17p, t(6;9), t(9;22) or complex karyotypes (greater than or equal to 3 unrelated abnormalities)
     • Eastern Cooperative Oncology Group status 2
3. Subjects have read and understood the Informed Consent Form
4. Subjects and their partners must be willing to avoid pregnancy during the trial and until 1 month after the last trial drug administration.

Exclusion Criteria:

Phase 1 and Phase 2:

1. Eastern Cooperative Oncology Group performance status 3 or greater,
2. Hyperleukocytosis with greater than 30x10 to the ninth power per L leukemia blasts in peripheral blood,
3. Acute promyelocytic leukemia
4. Administration of any antineoplastic therapy within at least 2 weeks
5. Participation in other clinical trials within at least 2 weeks of the first AS703026 dose,
6. Active central nervous system leukemia,
7. Active and uncontrolled infection
8. Other significant disease
9. Major surgery within two weeks prior to trial entry,
10. Liver function tests above specific limits
11. International normalized ratio greater than 1.5 x ULN unless on treatment with warfarin,
12. For female subjects: pregnant or breast-feeding,
13. Subjects with solid tumors, for whom the Investigator has clinical suspicion of active disease at the time of enrolment.
14. Legal incapacity or limited legal capacity.