Last updated: 11/03/2018 13:02:07
This product has been transferred to Novartis. GSK Clinical Study Register is no longer maintained for this study. The most up to date information is available on clinicaltrials.gov.
Eltrombopag Treatment of Thrombocytopenia in Subjects with advanced Myelodysplastic Syndrome (MDS) or secondary Acute Myeloid Leukemia after MDS (sAML/MDS)
Clinicaltrials.gov ID
EudraCT ID
EU CT Number
Not applicable
Trial status
No longer a GSK study
No longer a GSK study
Trial overview
Official title: 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)
Trial description: This study will evaluate the safety and tolerability of eltrombopag in the treatment of low platelet counts in adult subjects with advanced myelodysplastic syndrome (MDS), secondary acute myeloid leukemia after MDS (sAML/MDS), or de novo AML that are relapsed, refractory or ineligible to receive azacitidine, decitabine, intensive chemotherapy or autologous/allogeneic stem cell transplantation. This is a placebo-controlled study in which patients will receive study medication daily for 6 months, during which time the dose of study medication may be adjusted based upon individual platelet counts and bone marrow blast counts. All subjects will receive best standard of care (platelet transfusions, mild chemotherapy, cytokines, valproic acid, all-trans retinoic acid, ESAs or G-CSF) in addition to study medication. Subjects taking placebo may be allowed to crossover to eltrombopag treatment if a clinically and statistically significant improvement in bone marrow blast counts is seen in subjects treated with eltrombopag.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Allocation:
Randomized
Primary outcomes:
Safety and tolerability parameters including non-hematological laboratory Grade 3/Grade 4 toxicities, change in bone marrow blast counts from baseline and adverse events reporting.
Timeframe: Approximately 46 months
Secondary outcomes:
Proportion of subjects with a baseline platelet count <20 Gi/L and an increase to >20 Gi/L and by at least 2x baseline; or a baseline platelet count between >=20-<30 Gi/L and an absolute platelet count increase to >=50 Gi/L at any time during treatment.
Timeframe: Approx. 46 months
Frequency and number of units of platelet transfusions during the treatment and follow-up periods for eltrombopag- and placebo-treated subjects.
Timeframe: approx 46 months
The incidence and severity of bleeding events, measured using the World Health Organization (WHO) Bleeding Scale, during the treatment and 4 week follow-up periods for eltrombopag- and placebo-treated subjects.
Timeframe: approx. 46 months
Overall survival (OS) of eltrombopag- and placebo-treated subjects.
Timeframe: approx. 46 months
Change in health-related quality of life as measured using the EQ-5D questionnaire.
Timeframe: approx. 46 months
Interventions:
Drug: eltrombopag olamine
Other: Placebo
Enrollment:
98
Observational study model:
Not applicable
Primary completion date:
2012-26-06
Time perspective:
Not applicable
Clinical publications:
Mavroudi I, Pyrovolaki K, Pavlaki K, Kozana A, Psyllaki M, Kalpadakis C, Pontikoglou C, Papadaki HA. Effect of the nonpeptide thrombopoietin receptor agonist eltrombopag on megakaryopoiesis of patients with lower risk myelodysplastic syndrome. [Leuk Res]. 2010;35(3):323-328.
Mavroudi I, Pyrovolaki K, Pavlaki K, Kozana A, Psyllaki M, Kalpadakis C, Pontikoglou C, Papadaki HA. Effect of the nonpeptide thrombopoietin receptor agonist eltrombopag on megakaryopoiesis of patients with lower risk myelodysplastic syndrome. Leuk Res. 2010;35(3):323-328
Medical condition
Myelodysplastic syndrome
Product
eltrombopag
Collaborators
Not applicable
Study date(s)
May 2009 to December 2013
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- 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 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.
Inclusion and exclusion criteria
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.
Trial location(s)
Location
GSK Investigational Site
San Antonio, Texas, United States, 78229
Status
Study Complete
Location
GSK Investigational Site
Duisburg, Nordrhein-Westfalen, Germany, 47166
Status
Study Complete
Location
GSK Investigational Site
London, United Kingdom, SW17 0RE
Status
Terminated/Withdrawn
Location
GSK Investigational Site
St. Louis, Missouri, United States, 63110
Status
Study Complete
Location
GSK Investigational Site
Reggio Calabria, Calabria, Italy, 89100
Status
Study Complete
Location
GSK Investigational Site
Mainz, Rheinland-Pfalz, Germany, 55131
Status
Study Complete
Location
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19104
Status
Study Complete
Location
GSK Investigational Site
Greenville, South Carolina, United States, 29601
Status
Study Complete
Location
GSK Investigational Site
Koeln, Nordrhein-Westfalen, Germany, 50937
Status
Study Complete
Location
GSK Investigational Site
Aberdeen, United Kingdom, AB25 2ZN
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Stuttgart, Baden-Wuerttemberg, Germany, 70199
Status
Study Complete
Location
GSK Investigational Site
Rio de Janeiro, Rio De Janeiro, Brazil, 20211-030
Status
Study Complete
Location
GSK Investigational Site
Santa Monica, California, United States, 90404
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19106
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Boston, Massachusetts, United States, 02111
Status
Study Complete
Location
GSK Investigational Site
New Braunfels, Texas, United States, 78130
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Madison, Wisconsin, United States, 53705
Status
Study Complete
Location
GSK Investigational Site
Fairfax, Virginia, United States, 22031
Status
Study Complete
Location
GSK Investigational Site
Stanford, California, United States, 94305
Status
Study Complete
Location
GSK Investigational Site
Arlington, Virginia, United States, 22205
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Goettingen, Niedersachsen, Germany, 37075
Status
Study Complete
Location
GSK Investigational Site
Belo Horizonte, Minas Gerais, Brazil, 30130-100
Status
Study Complete
Location
GSK Investigational Site
Lake Worth, Florida, United States, 33467
Status
Study Complete
Location
GSK Investigational Site
Birmingham, Alabama, United States, 35294
Status
Study Complete
Location
GSK Investigational Site
Duesseldorf, Nordrhein-Westfalen, Germany, 40225
Status
Study Complete
Location
GSK Investigational Site
Baltimore, Maryland, United States, 21231
Status
Study Complete
Location
GSK Investigational Site
Coral Springs, Florida, United States, 33065
Status
Study Complete
Location
GSK Investigational Site
Detroit, Michigan, United States, 48202
Status
Study Complete
Location
GSK Investigational Site
Ulm, Baden-Wuerttemberg, Germany, 89081
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Pittsburgh, Pennsylvania, United States, 15224
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Memphis, Tennessee, United States, 38120
Status
Terminated/Withdrawn
Location
GSK Investigational Site
San Juan, Puerto Rico, Puerto Rico, 00927
Status
Study Complete
Location
GSK Investigational Site
Rio de Janeiro, Rio De Janeiro, Brazil, 20230 -130
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Camden, New Jersey, United States, 08103
Status
Study Complete
Location
GSK Investigational Site
Atlanta, Georgia, United States, 30341
Status
Study Complete
Location
GSK Investigational Site
Kansas City, Missouri, United States, 64128
Status
Study Complete
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
Protocol
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
No longer a GSK study
Actual primary completion date
2012-26-06
Actual study completion date
2013-05-12
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
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Additional information
Results for study 112509 can be found on the GSK Clinical Study Register.
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