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Myelodysplastic SyndromePhase 1NCT00903422

Eltrombopag Treatment of Thrombocytopenia in Subjects With Advanced Myelodysplastic Syndrome (MDS) or Secondary Acute Myeloid Leukemia After MDS (sAML/MDS)

A Phase 1 study testing eltrombopag olamine in people with Myelodysplastic Syndrome, run by GlaxoSmithKline at 65 sites in 11 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Myelodysplastic Syndrome
What is being tested?
eltrombopag olamine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
98 participants
Where
65 sitesin 11 countries
Study dates
14 May 2009to 5 Dec 2013
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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).

Who cannot join

  • 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).
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  • 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 locations and contacts

65 sites in 11 countries.

65 sites in 11 countries

United States24 sites

  • GSK Investigational Site

    Arlington, Virginia, 22205

  • GSK Investigational Site

    Atlanta, Georgia, 30341

  • GSK Investigational Site

    Baltimore, Maryland, 21231

  • GSK Investigational Site

    Birmingham, Alabama, 35294

  • GSK Investigational Site

    Boston, Massachusetts, 02111

  • GSK Investigational Site

    Camden, New Jersey, 08103

  • GSK Investigational Site

    Coral Springs, Florida, 33065

  • GSK Investigational Site

    Detroit, Michigan, 48202

  • GSK Investigational Site

    Fairfax, Virginia, 22031

  • GSK Investigational Site

    Greenville, South Carolina, 29601

  • GSK Investigational Site

    Houston, Texas, 77030

  • GSK Investigational Site

    Kansas City, Missouri, 64128

  • GSK Investigational Site

    Lake Worth, Florida, 33467

  • GSK Investigational Site

    Madison, Wisconsin, 53705

  • GSK Investigational Site

    Memphis, Tennessee, 38120

  • GSK Investigational Site

    New Braunfels, Texas, 78130

  • GSK Investigational Site

    Philadelphia, Pennsylvania, 19104

  • GSK Investigational Site

    Philadelphia, Pennsylvania, 19106

  • GSK Investigational Site

    Pittsburgh, Pennsylvania, 15224

  • GSK Investigational Site

    San Antonio, Texas, 78229

  • GSK Investigational Site

    Santa Monica, California, 90404

  • GSK Investigational Site

    St Louis, Missouri, 63110

  • GSK Investigational Site

    Stanford, California, 94305

  • GSK Investigational Site

    The Bronx, New York, 10461

Other trials in United States

Germany10 sites

  • GSK Investigational Site

    Berlin, 12200

  • GSK Investigational Site

    Cologne, North Rhine-Westphalia, 50937

  • GSK Investigational Site

    Dresden, Saxony, 01307

  • GSK Investigational Site

    Duisburg, North Rhine-Westphalia, 47166

  • GSK Investigational Site

    Düsseldorf, North Rhine-Westphalia, 40225

  • GSK Investigational Site

    Göttingen, Lower Saxony, 37075

  • GSK Investigational Site

    Mainz, Rhineland-Palatinate, 55131

  • GSK Investigational Site

    Munich, Bavaria, 81675

  • GSK Investigational Site

    Stuttgart, Baden-Wurttemberg, 70199

  • GSK Investigational Site

    Ulm, Baden-Wurttemberg, 89081

Other trials in Germany

France7 sites

  • GSK Investigational Site

    Bayonne, 64109

  • GSK Investigational Site

    Besançon, 25030

  • GSK Investigational Site

    Bobigny, 93009

  • GSK Investigational Site

    Caen, 14033

  • GSK Investigational Site

    Marseille, 13273

  • GSK Investigational Site

    Paris, 75571

  • GSK Investigational Site

    Toulouse, 31059

Other trials in France

United Kingdom5 sites

  • GSK Investigational Site

    Aberdeen, AB25 2ZN

  • GSK Investigational Site

    Glasgow, G12 0YN

  • GSK Investigational Site

    Leeds, LS9 7TF

  • GSK Investigational Site

    London, SE5 9RS

  • GSK Investigational Site

    London, SW17 0RE

Other trials in United Kingdom

Brazil4 sites

  • GSK Investigational Site

    Belo Horizonte, Minas Gerais, 30130-100

  • GSK Investigational Site

    Rio de Janeiro, 20211-030

  • GSK Investigational Site

    Rio de Janeiro, 20230 -130

  • GSK Investigational Site

    Salvador, Estado de Bahia, 41253-190

Other trials in Brazil

Taiwan4 sites

  • GSK Investigational Site

    Changhua, 500

  • GSK Investigational Site

    Taichung, 404

  • GSK Investigational Site

    Taipei, 100

  • GSK Investigational Site

    Taipei, 112

Other trials in Taiwan

Italy3 sites

  • GSK Investigational Site

    Florence, Tuscany, 50134

  • GSK Investigational Site

    Reggio Calabria, Calabria, 89100

  • GSK Investigational Site

    Vicenza, Veneto, 36100

Other trials in Italy

South Korea3 sites

  • GSK Investigational Site

    Seoul, 135-710

  • GSK Investigational Site

    Seoul, 137-701

  • GSK Investigational Site

    Seoul, 138-736

Other trials in South Korea

Denmark2 sites

  • GSK Investigational Site

    Koebenhavn Oe, 2100

  • GSK Investigational Site

    Odense C, 5000

Other trials in Denmark

Hong Kong2 sites

  • GSK Investigational Site

    Hong Kong

  • GSK Investigational Site

    Shatin, New Territories

Other trials in Hong Kong

Puerto Rico1 site

  • GSK Investigational Site

    San Juan, 00927

Other trials in Puerto Rico

About this study

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)

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.

Read the detailed description

A double-blind, randomized, placebo-controlled phase I/II study to evaluate the safety and tolerability of eltrombopag olamine, a thrombopoietin receptor agonist, administered for 6 months as oral tablets once daily in adult subjects with advanced MDS, sAML/MDS, or de novo AML. Study medication may be increased up to 300 mg (150 mg maximum dose for East Asian subjects), based upon individual platelet counts and bone marrow blast counts.

Being tested
eltrombopag olamine, Placebo
Keywords
Advanced Myelodysplastic Syndrome, Thrombocytopenia, sAML/MDS, Eltrombopag, TPO-R agonist, de novo AML, Thrombopoietin, MDS, Thrombopoietin receptor agonist, secondary Acute Myeloid Leukemia after MDS, Platelets
Medical subject headings
Myelodysplastic Syndromes, Thrombocytopenia, Jacobs syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • eltrombopag olamineDrug

    thrombopoietin receptor agonist

  • PlaceboOther

    Placebo tablets with no active pharmaceutical ingredient

Study groups in NCT00903422
Study groupRoleWhat they receive
EltrombopagActive comparatorEltrombopag
Receives: Drug: eltrombopag olamine
PlaceboPlacebo comparatorPlacebo
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Approximately 46 months

Secondary outcomes (5)

  1. 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.

    Measured: Approx. 46 months

  2. Frequency and number of units of platelet transfusions during the treatment and follow-up periods for eltrombopag- and placebo-treated subjects.

    Measured: approx 46 months

  3. 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.

    Measured: approx. 46 months

  4. Overall survival (OS) of eltrombopag- and placebo-treated subjects.

    Measured: approx. 46 months

  5. Change in health-related quality of life as measured using the EQ-5D questionnaire.

    Measured: approx. 46 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 May 2009 (estimated)
  2. Study start14 May 2009
  3. Primary completion26 Jun 2012
  4. Study completion5 Dec 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
98 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00903422
Sponsor's protocol ID
112509
Status last verified
Nov 2017
First submitted
14 May 2009
Last updated
13 Nov 2017
Results posted
No
Data monitoring committee
Yes

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. 2011 Mar;35(3):323-8. doi: 10.1016/j.leukres.2010.06.029. Epub 2010 Aug 4.

    PubMed 20688394

  • Platzbecker U, Wong RS, Verma A, Abboud C, Araujo S, Chiou TJ, Feigert J, Yeh SP, Gotze K, Gorin NC, Greenberg P, Kambhampati S, Kim YJ, Lee JH, Lyons R, Ruggeri M, Santini V, Cheng G, Jang JH, Chen CY, Johnson B, Bennett J, Mannino F, Kamel YM, Stone N, Dougherty S, Chan G, Giagounidis A. Safety and tolerability of eltrombopag versus placebo for treatment of thrombocytopenia in patients with advanced myelodysplastic syndromes or acute myeloid leukaemia: a multicentre, randomised, placebo-controlled, double-blind, phase 1/2 trial. Lancet Haematol. 2015 Oct;2(10):e417-26. doi: 10.1016/S2352-3026(15)00149-0. Epub 2015 Oct 1.

    PubMed 26686043

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing eltrombopag olamine in people with Myelodysplastic Syndrome, run by GlaxoSmithKline at 65 sites in 11 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 65 sites in United States, Germany, France, United Kingdom, Brazil and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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. (time frame: Approximately 46 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00903422, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2017.

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