| Inclusion Criteria: | 1) Female and male subjects with one of the following conditions: a. Primary or secondary AML pathologically confirmed according to WHO classification, who meet at least one of the following conditions: b. Subjects with second or subsequent relapse after standard therapy, for whom no established treatment options are available, c. Subjects refractory to available therapies, for example, who failed to achieve CR after 2 induction chemotherapy treatments, d. Newly-diagnosed older subjects (greater than or equal to 75 years of age), not candidates for intensive chemotherapy,
2) Subjects with MDS, IPSS Int-2 or high risk who are resistant or intolerant to standard treatment and are not candidates for transplantation,
3) Subjects with relapsed or refractory MM, who have failed or are intolerant to at least two prior therapies including thalidomide, lenalidomide and bortezomib,
4) Subjects with advanced myeloproliferative disorders (MPD) for whom no established treatment options are available,
5) Subjects with ALL, relapsed, refractory or intolerant to standard treatment and for whom no effective treatment options are available,
6) Age greater than or equal to 18 years,
7) Subjects have read and understood the Informed Consent Form and are willing and able to give informed consent. They fully understand requirements of the trial and are willing to comply with all trial visits and assessments,
8) Subjects and their partners must be willing to avoid pregnancy during the trial and until 1 month after the last trial drug administration. Males with female partners of childbearing potential and female subjects of childbearing potential must thereforebe willing to use adequate contraception as approved by the Investigator, such as oral contraceptives, two barrier methods or one barrier method with spermicide or intrauterine device, 2 weeks before, during the trial and 1 month after. For the purposes of this trial, childbearing potential is defined as "All female subjects after puberty unless
9) Continuation from Inclusion # 8. they are post-menopausal for at least two years, surgically sterile or sexually inactive".
10) Phase II Part: To be eligible for the inclusion into the Phase II part of this trial, the subjects must fulfill all of the following criteria, continued on #11
11) Female and male subjects with newly diagnosed primary or secondary AML pathologically confirmed according to WHO classification, who have NOT been exposed to any prior therapy for AML with the exception of (a) emergency leukapheresis and (b) emergency treatment for hyperleukocytosis with hydroxyurea that is allowed until 24 hours before the start of the trial treatment. Note: Prior therapy for preexisting hematological condition e.g. MDS or MPD, including but not limited to hypomethylating agents is allowed until at least 2 weeks or 5 half lives of that agent before the first dose of AS703026.
12) Subjects who meet at least one of the following conditions: Age greater than or equal to 75 years OR
13) Age greater than or equal to 60 and less than 75 years with at least one of the following poor prognostic factors continued on #14
14) a. Secondary AML, as determined by known and documented exposure to leukemogenic therapy or environmental toxin, b. antecedent history of MDS or myeloproliferative disorder according to WHO criteria for at least 3 months prior to trial entry, with prior bone marrow aspirate, biopsy and peripheral blood smear documenting the diagnosis, c. 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), d. ECOG Performance status 2.
15) Subjects have read and understood the Informed Consent Form and are willing and able to give informed consent. They fully understand requirements of the trial and are willing to comply with all trial visits and assessments.
16) Subjects and their partners must be willing to avoid pregnancy during the trial and until 1 month after the last trial drug administration. Males with female partners of childbearing potential must therefore be willing to use adequate contraception as approved by the Investigator, such as oral contraceptives, two barrier methods or one barrier method with spermicide or intrauterine device, 2 weeks before, during the trial and 1 month after.
17) Continued from #16. For the purposes of this trial, childbearing potential is defined as "All female subjects after puberty unless they are post-menopausal for at least two years, surgically sterile or sexually inactive". |