Eltrombopag for the Treatment of Thrombocytopenia Due to Low- and Intermediate Risk Myelodysplastic Syndromes

NCT ID: NCT02912208

Last Updated: 2022-01-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

174 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-06-11

Study Completion Date

2026-10-31

Brief Summary

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Myelodysplastic syndromes (MDS) prevail in older age and are characterized by ineffective erythropoiesis and peripheral cytopenias. Supportive therapy is the main therapeutic option for most patients. Quality of Life (QoL) is mainly deteriorated by anemia and by the limitations associated with thrombocytopenia, neutropenia and transfusion dependence. The only available treatment for severe thrombocytopenia, in the presence of bleeding, is platelet transfusion.

Eltrombopag is an orally bioavailable agonist of the thrombopoietin receptor. In adult patients with chronic immune thrombocytopenia (ITP), Eltrombopag rapidly increases platelet counts and significantly reduces bleeding episodes during treatment. Eltrombopag is well tolerated. In 2007, Eltrombopag has received the Orphan Drug Designation for the treatment of ITP (EMEA/OD/031/07), and in 2008 the Food and Drug Association approved Eltrombopag for the treatment of ITP refractory or resistant. It has been shown that in patients affected by MDS and by acute myeloid leukemia, Eltrombopag neither increases the proliferation, nor the clonogenic growth capacity of bone marrow blasts. Furthermore, Eltrombopag induces an increase in the megakaryocytic differentiation and in the formation of normal megakaryocytic colonies. These results provide the rationale for pursuing further research on Eltrombopag for the treatment of thrombocytopenia in case of MDS.

The study is open to adult patients with myelodysplastic syndrome (MDS) with thrombocytopenia and low- or intermediate-1 IPSS risk (Index Prognostic Score System).

Severe thrombocytopenia associated with MDS may lead to death from hemorrhage, even in low prognostic risk patients. The benefit of platelet transfusion is short-termed. Patients become refractory in the long term. The availability of a treatment that induces the increase of platelet count is extremely important, either in terms of quality of life, and in overall survival.

Detailed Description

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Conditions

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Myelodysplastic Syndromes Thrombocytopenia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

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Arm 1 (Eltrombopag)

Arm 1 is the active treatment arm

Group Type EXPERIMENTAL

Eltrombopag/Revolade

Intervention Type DRUG

Eltrombopag 50 mg once daily has been selected as the starting dose for this study. Thereafter, dependent on platelet response the dose of study medication can be increased by 50 mg every 2 weeks, up to a maximum dose of 300 mg once daily (150 mg in subjects of East Asian ethnicity).

Arm 2 (Placebo)

Arm 2 is the control arm

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

The administration is the same of eltrombopag

Interventions

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Eltrombopag/Revolade

Eltrombopag 50 mg once daily has been selected as the starting dose for this study. Thereafter, dependent on platelet response the dose of study medication can be increased by 50 mg every 2 weeks, up to a maximum dose of 300 mg once daily (150 mg in subjects of East Asian ethnicity).

Intervention Type DRUG

Placebo

The administration is the same of eltrombopag

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. Adult subjects (18 years of age or older) with low or intermediate-1 IPSS risk MDS and stable disease.
2. Subjects must have a platelet count taken within the 4 weeks prior to randomization that is \<30 Gi/L.
3. Subjects must be ineligible or relapsed or refractory to receive other treatment options (such as azacitidine or lenalidomide) and must be ineligible to receive intensive chemotherapy or autologous/allogeneic stem cell transplantation.
4. Subjects must have platelet count and platelet transfusion data available over a period of 8 weeks prior to randomization.
5. During the 2 months prior to randomization, subjects must have a baseline Bone Marrow examination which includes cytomorphology and cytogenetics. Histopathology should be performed.
6. Erythropoiesis-stimulating agents (ESAs) in anemic subjects or granulocyte colonystimulating 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.
7. ECOG (Eastern Cooperative Oncology Group) Performance Status 0-3
8. Subject is able to understand and comply with protocol requirements and instructions.
9. Subject has signed and dated informed consent.
10. Adequate baseline organ function defined by the criteria below:

total bilirubin (except for Gilbert's Syndrome) ≤ 1.5 x Upper Limit Normal Alanine aminotransferase and Aspartate aminotransferase ≤ 3 x Upper Limit Normal creatinine ≤ 2 x Upper Limit Normal albumin must not be below the lower limit of normal by more than 20%.
11. Subject is practicing an acceptable method of contraception. 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 of an highly effective method of contraception from 2 weeks prior to administration of study medication, throughout the study, and 28 days after completion or premature discontinuation from the study.

Exclusion Criteria

1. MDS with intermediate-2 or high IPSS risk.
2. History of treatment for cancer other than MDS with systemic chemotherapy and/or radiotherapy within the last 2 years.
3. History of treatment with romiplostim or other Thrombopoietin receptor agonists.
4. Pre-existing cardiovascular disease (including congestive heart failure, New York Heart Association Grade III/IV), or arrhythmia known to increase the risk of thromboembolic events (e.g. persistent atrial fibrillation), or subjects with a QTc \>450 msec (QTc \>480 msec for subjects with Bundle Branch Block).
5. BM fibrosis that leads to an inability to aspirate marrow for assessment.
6. Peripheral monocytosis \> 1000/uL prior to Day 1 of study medication.
7. Leukocytosis \>=25,000/uL prior to Day 1 of study medication.
8. 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.
9. Current alcohol or drug abuse.
10. Treatment with an Investigational Product 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).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Associazione Qol-one

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Esther Natalie Oliva

Role: STUDY_CHAIR

QOL-ONE Associazione Culturale e di Ricerca

Locations

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CHU Amiens

Amiens, , France

Site Status

Centre d'Avignon

Avignon, , France

Site Status

Hôpital de la Côte Basque

Bayonne, , France

Site Status

Centre d'Avicenne, Hôpital d'Avicenne

Bobigny, , France

Site Status

CHU de Haut-Lévèque

Bordeaux, , France

Site Status

Centre Hospitalier de Boulogne Sur Mer

Boulogne-sur-Mer, , France

Site Status

CHU Clémenceau

Caen, , France

Site Status

Centre Henri Mondor

Créteil, , France

Site Status

CHU de Grenoble

Grenoble, , France

Site Status

Centre Le Mans

Le Mans, , France

Site Status

Hôpital Saint Vincent de Paul

Lille, , France

Site Status

CHRU de Limoges

Limoges, , France

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Centre de Marseille

Marseille, , France

Site Status

CHU Brabois

Nancy, , France

Site Status

Centre de Nantes

Nantes, , France

Site Status

Hopital Archet 1

Nice, , France

Site Status

Centre Hospitalier Universitaire de Nimes

Nîmes, , France

Site Status

Centre de St Louis, Hôpital St Louis

Paris, , France

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Centre Hospitalier de la Région d'Annecy

Pringy, , France

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Centre de Rouen, Centre Henri Becquerel

Rouen, , France

Site Status

CHU Purpan

Toulouse, , France

Site Status

CHU de Bretonneau

Tours, , France

Site Status

Heinrich-Heine-Universität Düsseldorf

Düsseldorf, , Germany

Site Status

Universitätsmedizin Mannheim

Mannheim, , Germany

Site Status

A.O. SS. Antonio e Biagio e Cesare Arrigo

Alessandria, AL, Italy

Site Status

Ospedale Riuniti

Ancona, AN, Italy

Site Status

Ospedale Cardinal Massaia

Asti, AT, Italy

Site Status

A.O. S. Giovanni Moscati

Avellino, AV, Italy

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Policlinico Università di Bari

Bari, BA, Italy

Site Status

Ospedale A. Perrino

Brindisi, BR, Italy

Site Status

Ospedale "Roberto Binaghi"

Cagliari, CA, Italy

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Ospedale L'Annunziata

Cosenza, CS, Italy

Site Status

Ospedale Ferrarotto

Catania, CT, Italy

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Ospedale Garibaldi

Catania, CT, Italy

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Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, FG, Italy

Site Status

Azienda Ospedaliera Universitaria Careggi

Florence, FI, Italy

Site Status

Università degli Studi di Genova

Genova, GE, Italy

Site Status

Ospedale Vito Fazzi

Lecce, LE, Italy

Site Status

IRCCS Ospedale Maggiore Policlinico

Milan, MI, Italy

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Ospedale Niguarda

Milan, MI, Italy

Site Status

Ospedale Civile Spirito Santo

Pescara, PE, Italy

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Azienda Ospedaliera Bianchi-Melacrino-Morelli

Reggio Calabria, RC, Italy

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Arcispedale di Santa Maria Nuova

Reggio Emilia, RE, Italy

Site Status

A.O. San Camillo Forlanini

Roma, RM, Italy

Site Status

Ospedale Sant'Eugenio

Roma, RM, Italy

Site Status

Policlinico Agostino Gemelli

Roma, RM, Italy

Site Status

Università Campus Bio Medico di Roma

Roma, RM, Italy

Site Status

Azienda Ospedaliera Sant'Andrea

Rome, RM, Italy

Site Status

IRCCS Istituto Regina Elena

Rome, RM, Italy

Site Status

Ospedale Nuova Regina Margherita

Rome, RM, Italy

Site Status

Policlinico Umberto I

Rome, RM, Italy

Site Status

Policlinico Universitario Tor Vergata

Rome, RM, Italy

Site Status

A.O.U. San Giovanni di Dio e Ruggì D'Aragona

Salerno, SA, Italy

Site Status

Policlinico Santa Maria alle Scotte

Siena, SI, Italy

Site Status

A.O. Santa Maria

Terni, TE, Italy

Site Status

A.O. Citta' della Salute e della Scienza di Torino

Torino, TO, Italy

Site Status

U.O. Citta' della Salute e della Scienza di Torino

Torino, TO, Italy

Site Status

General Hospital Celje

Celje, , Slovenia

Site Status

Univerzitetni klinini center Ljubljana

Ljubljana, , Slovenia

Site Status

University Medical Centre Maribor

Maribor, , Slovenia

Site Status

General Hospital Murska Sobota

Murska Sobota, , Slovenia

Site Status

General Hospital Nova Gorica

Nova Gorica, , Slovenia

Site Status

General Hospital Novo mesto

Novo Mesto, , Slovenia

Site Status

General Hospital Slovenj Gradec

Slovenj Gradec, , Slovenia

Site Status

Countries

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France Germany Italy Slovenia

References

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Oliva EN, Riva M, Niscola P, Santini V, Breccia M, Giai V, Poloni A, Patriarca A, Crisa E, Capodanno I, Salutari P, Reda G, Cascavilla N, Ferrero D, Guarini A, Tripepi G, Ianni G, Russo E, Castelli A, Fattizzo B, Beltrami G, Bocchia M, Molteni A, Fenaux P, Germing U, Ricco A, Palumbo GA, Impera S, Di Renzo N, Rivellini F, Buccisano F, Stamatoullas-Bastard A, Liberati AM, Candoni A, Delfino IM, Arcadi MT, Cufari P, Rizzo L, Bova I, D'Errigo MG, Zini G, Latagliata R. Eltrombopag for Low-Risk Myelodysplastic Syndromes With Thrombocytopenia: Interim Results of a Phase II, Randomized, Placebo-Controlled Clinical Trial (EQOL-MDS). J Clin Oncol. 2023 Oct 1;41(28):4486-4496. doi: 10.1200/JCO.22.02699. Epub 2023 Jun 9.

Reference Type DERIVED
PMID: 37294914 (View on PubMed)

Other Identifiers

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EQoL-MDS

Identifier Type: -

Identifier Source: org_study_id

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