Please select the eligibility criteria that correspond to the clinical trial below.
Title: Study PMA112509, a Phase I/II Study of Eltrombopag in Thrombocytopenic Subjects With Advanced Myelodysplastic Syndrome (MDS) or Secondary Acute Myeloid Leukemia After MDS (sAML/MDS)
Brief Summary: This study will evaluate the safety and tolerability of eltrombopag in the treatment of low platelet counts in adult subjects with advanced myelodysplastic syndrome (MDS), secondary acute myeloid leukemia after MDS (sAML/MDS), or de novo AML that are relapsed, refractory or ineligible to receive azacitidine, decitabine, intensive chemotherapy or autologous/allogeneic stem cell transplantation. This is a placebo-controlled study in which patients will receive study medication daily for 6 months, during which time the dose of study medication may be adjusted based upon individual platelet counts and bone marrow blast counts. All subjects will receive best standard of care (platelet transfusions, mild chemotherapy, cytokines, valproic acid, all-trans retinoic acid, ESAs or G-CSF) in addition to study medication. Subjects taking placebo may be allowed to crossover to eltrombopag treatment if a clinically and statistically significant improvement in bone marrow blast counts is seen in subjects treated with eltrombopag.


Options:
A: Inclusion Criteria:

* 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).

Exclusion Criteria:

* Subjects with a diagnosis of acute promyelocytic leukemia.
* History of treatment for cancer (other than MDS, sAML/MDS, or de novo AML) with systemic chemotherapy and/or radiotherapy within the last 2 years.
* History of treatment with romiplostim or other TPO-R agonists.
* Pre-existing cardiovascular disease (including congestive heart failure, New York Heart Association \[NYHA\] Grade III/IV), or arrhythmia known to increase the risk of thromboembolic events (e.g. atrial fibrillation), or subjects with a QTc \>450 msec (QTc \>480 msec for subjects with Bundle Branch Block).
* Bone marrow fibrosis that leads to an inability to aspirate marrow for assessment.
* Spleen size \>14 cm (length as per ultrasound examination).
* Leukocytosis \>=25,000/uL prior to Day 1 of study medication.
* Female subjects who are nursing or pregnant (positive serum or urine Beta-human chorionic gonadotropin \[B-hCG\] pregnancy test) at screening or pre-dose on Day 1.
* Current alcohol or drug abuse.
* Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication.
* Active and uncontrolled infections.
* Subjects infected with Hepatitis B, C or Human Immunodeficiency Virus (HIV).
* Subjects with liver cirrhosis.
B: Inclusion Criteria:

* Diagnosis of MDS by bone marrow biopsy based on the World Health Organization (WHO) classification
* Low or Intermediate-1 risk category MDS using the IPSS
* Planned to receive lenalidomide 10 mg capsule by mouth daily for all 28 days of each cycle for at least 4 cycles
* Eastern Cooperative Oncology (ECOG) performance status of 0-2
* Subjects must be at least 18 years of age or older

Exclusion Criteria:

* Prior exposure to \>3 cycles of lenalidomide
* Exposure to lenalidomide within the last 30 days
* Prior history of leukemia or aplastic anemia
* Prior history of stem cell transplantation
* Prior malignancy (other than in situ cervical cancer or basal cell cancer of the skin) unless treated with curative intent and without evidence of disease for 3 years before randomization
* Active or uncontrolled infections
* Unstable angina, congestive heart failure \[NYHA \> class II\], uncontrolled hypertension \[diastolic \> 100 mmHg\], uncontrolled cardiac arrhythmia, or recent (within 1 year) myocardial infarction
* History of arterial thrombosis ( eg, stroke or transient ischemic attack) in the past year
* History of venous thrombosis in the past year
* Received IL-11 within 4 weeks of screening
* Less than 4 weeks since receipt of any investigational drug or device
* Have previously received any other thrombopoietic growth factor
* Pregnant or breast feeding
* Subjects of reproductive potential who are not using adequate contraceptive precautions, in the judgment of the investigator
* Known hypersensitivity to any recombinant E coli-derived product
C: Inclusion Criteria: - Diagnosis of MDS by bone marrow biopsy based on the World Health Organization (WHO) classification - Low, Intermediate-1 or Intermediate-2 risk category MDS using the IPSS (International Prognostic Scoring System) - Planned to receive either azacytidine 75 mg/m2 by subcutaneous administration each day for 7 days or decitabine 20 mg/m2 by intravenous administration each day for 5 days for at least 4 cycles Exclusion Criteria:

* Prior exposure to \>3 cycles hypomethylating agents
* Prior history of leukemia or aplastic anemia
* Prior history of bone marrow transplantation
* Prior malignancy (other than in situ cervical cancer or basal cell cancer of the skin) unless treated with curative intent and without evidence of disease for ³ 3 years before randomization
* Active or uncontrolled infections
* Unstable angina, congestive heart failure \[NYHA (New York Heart Association) \> class II\], uncontrolled hypertension \[diastolic \> 100 mmHg\], uncontrolled cardiac arrhythmia, or recent (within 1 year) myocardial infarction
* History of arterial thrombosis ( eg, stroke or transient ischemic attack) in the past year
* History of venous thrombosis that currently requires anti-coagulation therapy
* Received IL-11 within 4 weeks of screening
* Less than 4 weeks since receipt of any therapeutic drug or device that is not FDA approved for any indication
* Have previously received any other thrombopoietic growth factor
D: Inclusion Criteria:

* Must understand and voluntarily sign an informed consent form
* Age 18 years or older at the time of signing the informed consent
* Must be able to adhere to the study visit schedule and other protocol requirements.
* Diagnosis of low or intermediate-1-risk International Prognostic Scoring System (IPSS) Myelodysplastic Syndromes (MDS) without an abnormality of chromosome 5 involving a deletion between bands q31 and q33.
* Red blood cell (RBC) transfusion-dependent anemia defined as having received greater than or equal to 2 units of RBCs within 8 weeks of the first day of study drug treatment.
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.
* Women of childbearing potential (WCBP) must have a negative serum or urine pregnancy test within 7 days of starting study drug.
* Sexually active WCBP must agree to use adequate contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) while on study drug.
* WCBP must agree to have pregnancy tests every 4 weeks while on study drug.

Exclusion Criteria:

* Pregnant or lactating females
* Prior therapy with lenalidomide.
* An abnormality of chromosome 5 involving a deletion between bands q31 and q33.
* Lab Abnormality: Absolute neutrophil count (ANC) \<500 cell/mm\^3 (0.5\*10\^9/L)
* Lab Abnormality: Platelet count \<50,000/mm\^3 (50\*10\^9/L)
* Lab Abnormality: Serum creatinine \>2.5 mg/dL (221 mmol/L)
* Lab Abnormality: Serum total bilirubin \>2.0 mg/dL (34 mmol/L)
* Prior greater than or equal to grade 3 National Cancer Institute (NCI) Common Toxicity Criteria (CTC) allergic reaction/hypersensitivity to thalidomide.
* Clinically significant anemia due to factors such as iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis or gastrointestinal bleeding
* If a marrow aspirate is not evaluable for storage iron, transferrin saturation must be \> 20% and serum ferritin not less than 50 ng/mL
* Use of hematopoietic growth factors within 7 days of the first day of study drug treatment.
* Prior greater than or equal to grade 3 NCI CTC rash or any desquamation (blistering) while taking thalidomide.
* Chronic use (\>2 weeks) of greater than physiologic doses of a corticosteroid agent (dose equivalent to \>10 mg/day of prednisone) within 28 days of the first day of study drug treatment.
* Use of experimental or standard drugs (i.e. chemotherapeutic, immunosuppressive, and cytoprotective agents) for the treatment of MDS within 28 days of the first day of study drug treatment.
* Prior history of malignancy other than MDS (except basal cell or squamous cell carcinoma or carcinoma in situ of the cervix or breast) unless the subject has been free of disease for greater than or equal to 3 years.
* Use of any other experimental therapy within 28 days of the first day of study drug treatment.

Answer: A