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:

AML project

* inclusion in studies of the DSIL or OSHO group for AML
* AML M3/M3v can be included only when in complete remission
* age 16 - 80 years
* written informed consent

Autologous project

* AMl and ALL patients in first or second remission
* low grade or high grade non hodgkin lymphoma or morbus hodgkin or multiple myeloma
* conditioning regime: TBI 8-12 Gy/Cy 120 or BEAM or BU/CY or Melphalan 140-200mg/m2 or a similarly intensive chemotherapy regime
* age 16 - 65 years

Exclusion Criteria:

AML project

* known refractoriness to platelet transfusion
* known major bleeding with thrombocytopenia when the reason for bleeding is still ongoing
* known plasmatic coagulation disorder
* patient unable to give informed consent

Autologous project

* known refractoriness to platelet transfusion
* known major bleeding with thrombocytopenia when the reason for bleeding is still ongoing
* known plasmatic coagulation disorder
* patient unable to give informed consent
* patients with pulmonal or cerebral lesions due to infection or neoplasm
* patients with al-amyloidosis
B: Inclusion Criteria:

* Patients with hypoproliferative thrombocytopenia who are expected to have a platelet count of ≤ 10,000/µL (10x10\^9/L) for ≥ 10 days (Note: the prophylactic platelet trigger may be higher than10,000/µL (10x10\^9/L) in some participating institutions; however, the patient will still be eligible for participation as long as they are expected to be thrombocytopenic for 10 days)
* Must be an inpatient.
* Weight between 40 and 100 kg.

Exclusion Criteria:

* Diagnosis of promyelocytic leukemia.
* A history or current diagnosis of immune thrombocytopenia (ITP), thrombotic thrombocytopenia (TTP), or hemolytic uremia syndrome (HUS).
* Evidence of ≥ WHO Grade 2 bleeding while being assessed for the study entry.
* Patients who will receive bedside Leukoreduced platelet transfusions.
* Patients who are pregnant.
C: * INCLUSION CRITERIA:

  1. Diagnosis of aplastic anemia, with refractory thrombocytopenia following at least one treatment course of horse or rabbit ATG/cyclosporine.
  2. Platelet count less than or equal to 30,000/microL
  3. Age greater than or equal to 12 years old

EXCLUSION CRITERIA:

1. Diagnosis of Fanconi anemia
2. Infection not adequately responding to appropriate therapy
3. Patients with a PNH clone size in neutrophils of greater than or equal to 50%
4. HIV positivity
5. Creatinine \> 2.5
6. Bilirubin \> 2.0
7. SGOT or SGPT \> 5 times the upper limit of normal
8. Hypersensitivity to eltrombopag or its components
9. Female subjects who are nursing or pregnant or are unwilling to take oral contraceptives or refrain from pregnancy if of childbearing potential
10. History of malignancy other than localized tumors diagnosed more than one year previously and treated surgically with curative intent (for instance squamous cell or other skin cancers, stage 1 breast cancer, cervical carcinoma in situ, etc)
11. Unable to understand the investigational nature of the study or give informed consent
12. History of congestive heart failure arrhythmia requiring chronic treatment, arterial or venous thrombosis (not excluding line thrombosis) within the last 1 year, or myocardial infarction within 3 months before enrollment
13. ECOG Performance Status of 3 or greater
14. Treatment with horse or rabbit ATG or Campath within 6 months of study entry. Concurrent stable treatment with cyclosporine or G-CSF is permitted.
D: 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

Answer: D