Eltrombopag Treatment of Thrombocytopenia in Subjects With Advanced Myelodysplastic Syndrome (MDS) or Secondary Acute Myeloid Leukemia After MDS (sAML/MDS)

Adult subjects (18 years of age or older) with advanced MDS, sAML/MDS, or de novo AML with \>=10% and \<=50% blasts in bone marrow. Peripheral blood blast change over time should not be suggestive of highly proliferative disease (as judged by the investigator).

Subjects must be dependent on regular platelet transfusions or have a platelet count taken within the 4 weeks prior to randomization that is \<30 Gi/L.

Subjects must be relapsed, refractory or ineligible to receive standard treatment options of azacitidine and decitabine and must be relapsed, refractory or ineligible to receive intensive chemotherapy or autologous/allogeneic stem cell transplantation. A subject may be considered relapsed/refractory to a standard treatment if it is discontinued due to lack of efficacy. For subjects ineligible for standard treatments, it is permissible to start one of these standard treatments while on study medication if the Investigator considers that the subject becomes eligible during the course of the study.

Prior therapy with demethylating agents (azacitidine or decitabine), lenalidomide or IL-11(oprelvekin) must have been completed at least 4 weeks before Day 1; antithymocyte/antilymphocyte globulin, intensive chemotherapy, or autologous/allogeneic stem cell transplantation must have been completed at least 2 months before Day 1. If a subject must discontinue a course of therapy due to lack of efficacy, the washout periods listed above do not apply (and the patient may be screened and randomized immediately if other eligibility criteria are met).

Subjects must have platelet count and platelet transfusion data available over a period of 4 weeks prior to randomization.

Subjects with advanced MDS, sAML/MDS, or de novo AML must have stable disease indicated by a doubling time of peripheral blast counts \>7 days during screening.

During the 4 weeks prior to randomization, subjects must have a baseline bone marrow examination including the following:

cytomorphology to confirm bone marrow blasts between 10-50%,

cytogenetics (provide only most prevalent abnormal clone),

The results of the above tests are required prior to subject randomization.

Supportive/palliative therapies such as cytokines (except for IL-11; oprelvekin), valproic acid, all-trans retinoic acid or mild chemotherapy are allowed if part of the local SOC, provided those therapies have been at a stable dose for 4 weeks. If the subject chooses to discontinue these therapies prior to study entry, they must be completed 4 weeks prior to enrollment into this study, unless the therapy is discontinued due to lack of efficacy. Erythropoiesis-stimulating agents (ESAs) in anemic subjects or granulocyte colony-stimulating factor (G-CSF) in subjects with severe neutropenia and recurrent infections are allowed during the study as per accepted standards. Subjects who enter the study on ESAs or G-CSF should continue at the same dose schedule until the optimal dose of study medication has been established.

ECOG Status 0-3.

Subject is able to understand and comply with protocol requirements and instructions.

Subject has signed and dated informed consent.

Prothrombin time (PT/INR) and activated partial thromboplastin time (aPTT) must be within 80 to 120% of the normal range at baseline.

Adequate baseline organ function defined by the criteria below:

total bilirubin (except for Gilbert's Syndrome) \<= 1.5xULN

ALT and AST \<= 3xULN

creatinine \<= 2xULN

albumin must not be below the lower limit of normal (LLN) by more than 20%.

Subject is practicing an acceptable method of contraception (documented in chart). Female subjects (or female partners of male subjects) must either be of non-childbearing potential (hysterectomy, bilateral oophorectomy, bilateral tubal ligation or post-menopausal \>1 year), or of childbearing potential and use 1 of the following highly effective methods of contraception (i.e., Pearl Index \<1.0%) from 2 weeks prior to administration of study medication, throughout the study, and 28 days after completion or premature discontinuation from the study:

Complete abstinence from intercourse;

Intrauterine device (IUD);

Two forms of barrier contraception (diaphragm plus spermicide, and for males condom plus spermicide);

Male partner is sterile prior to entry into the study and is the only partner of the female;

Systemic contraceptives (combined or progesterone only).

What this study is about