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:

In order to be eligible for study entry, subjects must comply with the following:

* Males from 3 months old to 80 years old
* Signed written informed consent obtained prior to study entry
* Clinical diagnosis of WAS or XLT
* Platelet levels less than 100 x 109/L
* Adequate renal and hepatic function (creatinine and bilirubin less than or equal to 1.5 x IULN, AST and ALT less than or equal to 2.5 x IULN)

Exclusion Criteria:

Any patient is ineligible for study entry if he/she:

* Over the age of 80
* Women (only males are eligible)
* fertile men who are not practicing or who are unwilling to practice birth control while enrolled in the study or until at least 6 months after treatment
* Aspirin, aspirin-containing compounds, salicylates, non-steroidal anti-inflammatory medications (NSAIDS), clopidogrel or ticlopidine, warfarin or other vitamin K antagonists, unfractionated or low molecular heparin within 7 days of first infusion
* Red blood cell transfusion in the past four weeks
* Elevated (\> 1.5 x ULN) prothrombin time (PT) or partial thromboplastin time (PTT)
* New York Heart Classification III or IV heart disease. Other severe cardiovascular or cardiopulmonary disease, including COPD.
* Known HIV infection, hepatitis B or C infection
* Any infection requiring antibiotic treatment within 3 days
* Other concurrent medical or psychiatric conditions that, in the Investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations.
* Prior malignancy with less than a 5-year disease-free interval, excluding nonmelanoma skin cancers and carcinoma in situ of the cervix
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:

* 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
D: Inclusion Criteria:

Patients are eligible for this trial if:

1. Aged ≥18 years of age
2. Confirmed diagnosis of a haematological malignancy
3. Undergoing chemotherapy, or chemotherapy is planned, or haematopoietic stem cell transplantation
4. Anticipated to have a hypoproliferative thrombocytopenia resulting in a platelet count of ≤10x10⁹/L for ≥ 5 days
5. Able to comply with treatment and monitoring

Exclusion Criteria:

A patient will not be eligible for this trial if he/she fulfils one or more of the following criteria:

1. Patients with a past history or current diagnosis of arterial or venous thromboembolic disease including myocardial infarction, peripheral vascular disease and retinal arterial or venous thrombosis.
2. Diagnosis of acute promyelocytic leukaemia (APML) and undergoing induction chemotherapy
3. Patients with a diagnosis/previous history of veno-occlusive disease (also called sinusoidal obstruction syndrome)
4. Patients with known inherited or acquired prothrombotic disorders e.g.

   1. Lupus anticoagulant
   2. Positive antiphospholipids
5. Patients receiving any pro-coagulant agents (e.g. DDAVP, recombinant Factor VIIa or Prothrombin Complex Concentrates (PCC) within 48 hours of enrolment, or with known hypercoagulable state
6. Patients receiving L-asparaginase as part of their current cycle of treatment
7. History of immune thrombocytopenia (ITP), thrombotic thrombocytopenic purpura (TTP) or haemolytic uraemic syndrome (HUS)
8. Patients with overt disseminated intravascular coagulation (DIC) (See Appendix 3 in the protocol for definition)
9. Patients requiring a platelet transfusion threshold \>10x10/⁹L at time of randomisation. (This refers to patients who require their platelet count to be maintained at a certain specified level on an ongoing basis, and excludes a transient rise in the threshold due to sepsis.)
10. Patients with a known inherited or acquired bleeding disorder e.g.

    1. Acquired storage pool deficiency
    2. Paraproteinaemia with platelet inhibition
11. Patients receiving anticoagulant therapy or anti-platelet therapy
12. Patients with visible haematuria at time of randomisation
13. Patients with anuria (defined as urine output \< 10 mls/hr over 24 hours).
14. Patients with severe renal impairment (eGFR ≤30 ml/min/1.73m²)
15. Patients with a previous history of epilepsy, convulsions, fits or seizures
16. Patients who are pregnant or breast-feeding
17. Allergic to tranexamic acid.
18. Patients enrolled in other trials involving platelet transfusions, anti-fibrinolytics, platelet growth factors or other pro-coagulant agents.
19. Patients previously randomised into this trial at any stage of their treatment.

Answer: B