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)

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 90

Inclusion Criteria

1. 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).

2. 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.

3. 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.

4. 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).

5. Subjects must have platelet count and platelet transfusion data available over a
period of 4 weeks prior to randomization.

6. 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.

7. During the 4 weeks prior to randomization, subjects must have a baseline bone
marrow examination including the following:
a. cytomorphology to confirm bone marrow blasts between 10-50%,
b. cytogenetics (provide only most prevalent abnormal clone),
The results of the above tests are required prior to subject randomization

8. 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-timulatingagents (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.
9. ECOG Status 0-3.
10. Subject is able to understand and comply with protocol requirements and
instructions.
11. Subject has signed and dated informed consent.
12. Prothrombin time (PT/INR) and activated partial thromboplastin time (aPTT) must
be within 80 to 120% of the normal range at baseline.
13. Adequate baseline organ function defined by the criteria below:
•total bilirubin (except for Gilbert’s Syndrome) <=1.5xULN
•ALT and AST <=3xULN
•creatinine

Exclusion Criteria

1. Subjects with a diagnosis of acute promyelocytic leukemia.
2. History of treatment for cancer (other than MDS, sAML/MDS or or de novo AML) with systemic chemotherapy and/or radiotherapy within the last 2 years.
3. History of treatment with romiplostim or other TPO-R agonists.
4. 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).
5. Bone marrow fibrosis that leads to an inability to aspirate marrow for assessment.
6. Spleen size >14 cm (length as per ultrasound examination).
7. Leukocytosis =25,000/uL prior to Day 1 of study medication.
8. Female subjects who are nursing or pregnant (positive serum or urine ß-human
chorionic gonadotropin [ß-hCG] pregnancy test) at screening or pre-dose on Day 1.
9. Current alcohol or drug abuse.
10. Treatment with an investigational drug within 30 days or 5 half-lives (whichever is
longer) preceding the first dose of study medication.
11. Active and uncontrolled infections.
12. Subjects infected with Hepatitis B, C or Human Immunodeficiency Virus (HIV).
13. Subjects with liver cirrhosis.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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