Please select the eligibility criteria that correspond to the clinical trial below.
Title: An Open Label, Sequential Cohort, Dose Escalation Study to Evaluate the Safety and Efficacy of AMG 531 in Thrombocytopenic Subjects With Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)
Brief Summary: The purpose of this study is to evaluate the safety and tolerability of romiplostim in thrombocytopenic patients with low or Intermediate-1 risk MDS. In addition, the study will evaluate the platelet response to romiplostim.


Options:
A: Inclusion Criteria:

* Have a diagnosis of refractory anemia with excess blasts or refractory anemia with excess blasts in transformation according to the French-American-British classification system for myelodysplastic syndromes (MDS) and a relatively high risk of acute myeloid leukemia (AML) transformation, with an International Prognostic Scoring System score of INT-2 or High.
* Be 18 years of age or older
* Have a life expectancy of at least 3 months
* Be unlikely to proceed to bone marrow or stem cell transplantation therapy following remission
* Have serum bilirubin levels less than or equal to 1.5 times the upper limit of normal range for the laboratory
* Have serum glutamic-oxaloacetic transaminase (aspartate aminotransferase) or serum glutamic-pyruvic transaminase (alanine aminotransferase) levels less than or equal to 2 times the upper limit of normal (unless these are considered to be related to transfusion-induced secondary hemosiderosis)
* Have serum creatinine levels less than or equal to 1.5 times the upper limit of normal

Exclusion Criteria:

* Secondary myelodysplastic syndromes (MDS)
* Prior treatment with azacitidine;
* Prior history of acute myeloid leukemia (AML);
* Malignant disease diagnosed within prior 12 months;
* Metastatic disease;
* Hepatic tumors;
* Radiation, chemotherapy, cytotoxic therapy for non-MDS conditions within prior 12 months;
* Prior transplantation or cytotoxic therapy to treat MDS;
* Serious medical illness likely to limit survival to 12 months or less;
* Treatment with erythropoietin or myeloid growth factors during prior 21 days or androgenic hormones during prior 13 days;
* Active HIV, viral hepatitis type B or C;
* Treatment with investigational drugs during prior 30 days;
* Within the 28-day screening period, documented red cell folate deficiency, as evidenced by red blood cell folate (not serum folate) or vitamin B12 deficiency
B: Inclusion Criteria:

* Diagnosis of MDS using the World Health Organization classification
* Low or Intermediate-1 risk MDS using the International Prognostic Scoring System (IPSS)
* The mean of two platelet counts taken during the screening period must be ≤ 50 x 10\^9/L, with no individual count \> 55 x 10\^9/L (The mean platelet counts of 5 subjects enrolled at the maximum tolerated dose (MTD) must be ≤ 20 x 10\^9/L). Standard of care platelet assessments taken prior to Informed Consent may be used as 1 of the 2 counts taken within 3 weeks prior to study day 1.
* Must be ≥ 18 years of age at the time of obtaining informed consent
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at the time of screening
* Adequate Liver Function, as evidenced by a serum bilirubin ≤ 1.5 times the laboratory normal range (except for patients with a confirmed diagnosis of Gilbert's Disease), alanine aminotransferase (ALT) ≤ 3 times the laboratory normal range, and aspartate aminotransferase (AST) ≤ 3 times the laboratory normal range
* A serum creatinine concentration ≤ 2 mg/dL (≤ 176.6 µmol/L)
* Before any study-specific procedure, the appropriate written informed consent must be obtained (see Section 12.1)

Exclusion Criteria:

* Currently receiving any treatment for MDS other than transfusions and erythropoietic growth factors. If granulocyte growth factors are currently being received, they cannot be used on or after study day 1
* Clinically significant bleeding within 2 weeks prior to screening (eg, gastrointestinal (GI) bleeds, intracranial hemorrhage)
* Prior malignancy (other than controlled prostate cancer, 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 screening
* Prior history of bone marrow transplantation
* Persistent peripheral blood monocytosis (≥ 3 months with an absolute monocyte count \> 1,000/µL)
* Unstable angina, congestive heart failure (New York Heart Association \[NYHA\] \> class II), uncontrolled hypertension (diastolic \> 100 mmHg), uncontrolled cardiac arrhythmia, or recent (within 1 year) myocardial infarction
* Received Anti-Thymocyte Globuline (ATG) within 6 months of screening
* Received hypomethylating agents, immunomodulating agents, histone deacetylase inhibitors, cyclosporine or mycophenolate within 6 weeks of screening
* Received interleukin (IL)-11 (oprelvekin) within 4 weeks before screening
* Concurrent use of granulocyte growth factors (i.e. granulocyte-colony stimulating factor \[G-CSF; Neupogen, Granocyte\], pegfilgrastim \[Neulasta\], granulocyte macrophage-colony stimulating factor \[GM-CSF; Leukine, Prokine, Sargramostim\])
* Have ever previously received recombinant thrombopoietin (rTPO), pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), eltrombopag, or romiplostim
* Less than 4 weeks since receipt of any therapeutic drug or device that is not Food and Drug Administration (FDA) approved for any indication
* Other investigational procedures are excluded
* History of arterial thrombosis (eg, stroke or transient ischemic attack) in the past year
* History of venous thrombosis that currently requires anti-coagulation therapy
* Untreated B12 or folate deficiency
* Subject is evidently pregnant (eg, positive human chorionic gonadotropin \[HCG\] test) or is breast feeding
* Subject is not using adequate contraceptive precautions
* Subject has known hypersensitivity to any recombinant E coli-derived product
* Subject previously has enrolled in this study
* Subject will not be available for follow-up assessment
* Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures
C: 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.
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: B