Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Placebo Controlled Study Evaluating the Efficacy and Safety of AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Refractory to Splenectomy
Brief Summary: The purpose of this study is to evaluate the efficacy of AMG 531 in the treatment of thrombocytopenia in subjects with ITP as measured by the platelet response. This study will also evaluate changes in Patient Reported Outcomes and Health Resource Utilization due to treatment with AMG 531.


Options:
A: Inclusion Criteria:

* Diagnosis of ITP according to American Society of Hematology (ASH) guidelines (Appendix F)
* Have completed as least 1 prior treatment for ITP (e.g., prednisone)
* Subjects greater than 60 years of age must have a documented history of chronic ITP with a bone marrow report to confirm the diagnosis
* The platelet count (calculated from the mean of the 2 counts taken during the screening and pre-treatment periods) must be:

  \*less than 30 x 10\^9/L for those subjects not receiving any ITP therapy, with no count greater than 35 x 10\^9/L \*less than 50 x 10\^9/L for those subjects receiving a constant dose schedule of corticosteroids, azathioprine or danazol with no count greater than 55 x 10\^9/L
* A serum creatinine concentration less than or equal to 2 mg/dl (less than or equal to 176.8 µmol/L)
* Adequate liver function, as evidenced by a serum bilirubin less than or equal to 1.5 times the laboratory normal range
* Hemoglobin greater than 11.0 g/dL
* Written informed consent (see Section 12.1)

Exclusion Criteria:

* Have had a Splenectomy for any reason
* Any known history of bone marrow stem cell disorder (Any abnormal bone marrow findings other than those typical of ITP must be approved by Amgen before a subject may be enrolled in the study)
* Any active malignancy. If prior history of cancer other than basal cell carcinoma or cervical carcinoma in situ, no treatment or active disease within 5 years before randomization
* Documented diagnosis of arterial thrombosis (i.e., stroke, transient ischemic attack or myocardial infarction) in the past year
* History of venous thrombosis (i.e., deep vein thrombosis, pulmonary embolism) including those subjects who are on ant-coagulation therapy
* Unstable or uncontrolled disease or condition related to or impacting cardiac function (e.g., unstable angina, congestive heart failure \[NYHA greater than class II\], uncontrolled hypertension \[diastolic greater than 100 mmHg\] or cardiac arrhythmia)
* Have 3 or more of the following predisposing factors for thromboembolic events: diabetes; smoker; using oral contraceptives; on estrogen therapy; known positive for anti-phospholipid antibodies; hypertriglyceridemia; hypercholesteremia (greater than 240 mg/dL); treatment for hypertension
* Known positive test for human immunodeficiency virus (HIV) infection or hepatitis C virus
* Currently receiving any treatment for ITP except corticosteroids, azathioprine or danazol administered at a constant dose and schedule
* IV Ig or anti-D Ig within 2 weeks before the screening visit
* Rituximab (for any indication) within 14 weeks before the screening visit or anticipated use during the time of the proposed study
* Received hematopoietic growth factors, including IL-11 (oprelvekin) within 4 weeks before the screening visit
* Past or present participation in any study evaluating PEG-rHuMGDF, recombinant human thrombopoietin (rHuTPO), AMG 531 or related platelet product
* Received any aklylating agents within 8 weeks before the screening visit or anticipated use during the time of the proposed study
* Less than 4 weeks since receipt of any therapeutic drug or device that is not FDA approved for any indication before the screening period - Less than 8 weeks since major surgery
* 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
* Concerns for subject's compliance with the protocol
B: Inclusion Criteria:

* Diagnosis of ITP according to American Society of Hematology (ASH) guidelines at least 3 months before enrollment
* Have completed at least 1 prior treatment for ITP
* Two (including day -2) of the 3 platelet counts taken during the screening and pre-treatment periods must have fulfilled the following:

  * less than 30 x 10\^9/L for those subjects not receiving any ITP therapy,
  * less than 50 x 10\^9/L for those subjects receiving any ITP therapy
* Eastern Cooperative Oncology Group performance status of 0 to 2
* Serum creatinine concentration ≤ 2 mg/dL (≤ 176.8 µmol/L)
* Adequate liver function, as evidenced by a serum bilirubin ≤ 1.5 times the laboratory normal range
* Hemoglobin greater than 10.0 g/dL
* Written informed consent

Exclusion Criteria:

* Considered a substantial risk for adverse outcomes because of a clinically important trend (as determined by the investigator) detected in the platelet counts during the screening period
* Any known history of bone marrow stem cell disorder
* Any active malignancy. If prior history of cancer other than basal cell carcinoma or cervical carcinoma in situ, no treatment or active disease within 5 years before randomization
* Documented diagnosis of arterial thrombosis (ie, stroke, transient ischemic attack, or myocardial infarction) in the previous year; history of venous thrombosis (ie, deep vein thrombosis, pulmonary embolism) and receiving anticoagulation therapy
* Unstable or uncontrolled disease or condition related to or impacting cardiac function (e.g., unstable angina, congestive heart failure \[New York Heart Association (NYHA) greater than class II\], uncontrolled hypertension \[diastolic greater than 100 mmHg\] or cardiac arrhythmia)
* Have 3 or more of the following predisposing factors for thromboembolic events: diabetes; smoker using oral contraceptives; hypercholesteremia (\> 240 mg/dL); treatment for hypertension
* Known positive test for human immunodeficiency virus (HIV) infection or hepatitis C virus
* Received any treatment for ITP (except for a constant dose schedule of corticosteroids) within 4 weeks before the screening visit
* Received intravenous (IV) immunoglobulin (Ig) or WinRho within 2 weeks before the screening visit
* Received hematopoietic growth factors, including interleukin (IL)-11 (Neumega®) within 4 weeks before the screening visit
* Past or present participation in any study evaluating polyethylene glycol recombinant human magakaryopoiesis differentiating factor (PEG-rHuMGDF), recombinant human thrombopoietin (rHuTPO), or related platelet product
* Received any alkylating agents within 8 weeks before the screening visit or anticipated use during the time of the proposed study
* Received any monoclonal antibody (eg, rituximab) within 16 weeks before the screening visit or anticipated use during the time of the proposed study
* Less than 4 weeks since receipt of any therapeutic drug or device that is not FDA approved for any indication before the screening period
* Less than 2 months since major surgery (including laparoscopic splenectomy)
* Pregnant or breast feeding
* Subjects of reproductive potential who are not using adequate contraceptive precautions, in the judgment of the investigator
C: Inclusion Criteria:

* Subjects must be enrolled in AMG 531 protocol 20030105 or 20030212
* Subject must have had a bone marrow biopsy within one year of enrollment (with available tissue block to send to a central pathology laboratory for interpretation) or must consent to a pre-treatment bone marrow biopsy and aspirate
* Written informed consent

Exclusion Criteria:

* 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
D: Inclusion Criteria:

* Diagnosis of ITP according to American Society of Hematology (ASH) guidelines (Appendix F)
* Have had a splenectomy for the treatment of ITP greater than or equal to 24 weeks prior to study entry
* Subjects greater than 60 years of age must have a documented history of chronic ITP with a bone marrow report to confirm the diagnosis
* The platelet count (calculated from the mean of the 2 counts taken during the screening and pre-treatment periods) must be:
* \* less than 30 x 10\^9/L for those subjects not receiving any ITP therapy, with no count greater than 35 x 10\^9/L,
* \* less than 50 x 10\^9/L for those subjects receiving a constant dose schedule of corticosteroids, azathioprine or danazol with no count greater than 55 x 10\^9/L
* A serum creatinine concentration less than or equal to 2 mg/dl(less than or equal to 176.8 µmol/L)
* Adequate liver function, as evidenced by a serum bilirubin less than or equal to 1.5 times the laboratory normal range
* Hemoglobin greater than 11.0 g/dL
* Written informed consent (see Section 12.1)

Exclusion Criteria:

* Any known history of bone marrow stem cell disorder (Any abnormal bone marrow findings other than those typical of ITP must be approved by Amgen before a subject may be enrolled in the study)
* Any active malignancy. If prior history of cancer other than basal cell carcinoma or cervical carcinoma in situ, no treatment or active disease within 5 years before randomization
* Documented diagnosis of arterial thrombosis (i.e., stroke, transient ischemic attack or myocardial infarction) in the past year
* History of venous thrombosis (i.e., deep vein thrombosis, pulmonary embolism) including those subjects who are on ant-coagulation therapy
* Unstable or uncontrolled disease or condition related to or impacting cardiac function (e.g., unstable angina, congestive heart failure \[NYHA greater than class II\], uncontrolled hypertension \[diastolic greater than 100 mmHg\] or cardiac arrhythmia)
* Have 3 or more of the following predisposing factors for thromboembolic events: diabetes; smoker; using oral contraceptives; on estrogen therapy; known positive for anti-phospholipid antibodies; hypertriglyceridemia; hypercholesteremia (greater than 240 mg/dL); treatment for hypertension
* Known positive test for human immunodeficiency virus (HIV) infection or hepatitis C virus
* Currently receiving any treatment for ITP except corticosteroids, azathioprine or danazol administered at a constant dose and schedule
* IV Ig or anti-D Ig within 2 weeks before the screening visit
* Rituximab (for any indication) within 14 weeks before the screening visit or anticipated use during the time of the proposed study
* Received hematopoietic growth factors, including IL-11 (oprelvekin) within 4 weeks before the screening visit
* Past or present participation in any study evaluating PEG-rHuMGDF, recombinant human thrombopoietin (rHuTPO), AMG 531 or related platelet product
* Received any aklylating agents within 8 weeks before the screening visit or anticipated use during the time of the proposed study
* Less than 4 weeks since receipt of any therapeutic drug or device that is not FDA approved for any indication before the screening period
* Less than 8 weeks since major surgery
* 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
* Concerns for subject's compliance with the protocol

Answer: D