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

NCT02912208 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: EQoL-MDS
• Study Type: interventional
• Target: 174
• Locations: 4 countries
• Sites: 64

Brief Summary

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.

Conditions

Myelodysplastic Syndromes; Thrombocytopenia

Outcome Measures

Primary Outcomes (4)

• Response rate

  Proportion of patients achieving a complete response (CR) or response (R) during the treatment period

  Six months

• Safety and Tolerability (number of adverse events)

  Safety and tolerability in terms of frequency of adverse events (AE) and serious adverse events (SAE)

  Six month

• Duration of platelet response

  five years

• long-term safety and tolerability (number adverse events in the long term)

  Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 and number of adverse events reporting in accordance with CTCAE v4.0

  five years

Secondary Outcomes (7)

• Quality of life (QoL) score

  six months

• number of monthly platelet transfusions

  six months

• duration of transfusion independence

  six months

• time to response

  six months

• incidence and severity of bleeding

  six months

Study Arms (2)

Arm 1 (Eltrombopag)

EXPERIMENTAL

Arm 1 is the active treatment arm

Drug: Eltrombopag/Revolade

Arm 2 (Placebo)

PLACEBO COMPARATOR

Arm 2 is the control arm

Other: Placebo

Interventions

Eltrombopag/Revolade 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 1 (Eltrombopag)

Placebo OTHER

The administration is the same of eltrombopag

Arm 2 (Placebo)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult subjects (18 years of age or older) with low or intermediate-1 IPSS risk MDS and stable disease.
• Subjects must have a platelet count taken within the 4 weeks prior to randomization that is \<30 Gi/L.
• 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.
• Subjects must have platelet count and platelet transfusion data available over a period of 8 weeks prior to randomization.
• During the 2 months prior to randomization, subjects must have a baseline Bone Marrow examination which includes cytomorphology and cytogenetics. Histopathology should be performed.
• 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.
• ECOG (Eastern Cooperative Oncology Group) Performance Status 0-3
• Subject is able to understand and comply with protocol requirements and instructions.
• Subject has signed and dated informed consent.
• 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%.
• 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.

You may not qualify if:

• MDS with intermediate-2 or high IPSS risk.
• History of treatment for cancer other than MDS with systemic chemotherapy and/or radiotherapy within the last 2 years.
• History of treatment with romiplostim or other Thrombopoietin receptor agonists.
• 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).
• BM fibrosis that leads to an inability to aspirate marrow for assessment.
• Peripheral monocytosis \> 1000/uL prior to Day 1 of study medication.
• 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 Product 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).

Sponsors & Collaborators

• Associazione Qol-one: lead

Study Sites (64)

CHU Amiens

Amiens, France

Location

Centre d'Avignon

Avignon, France

Location

Hôpital de la Côte Basque

Bayonne, France

Location

Centre d'Avicenne, Hôpital d'Avicenne

Bobigny, France

Location

CHU de Haut-Lévèque

Bordeaux, France

Location

Centre Hospitalier de Boulogne Sur Mer

Boulogne-sur-Mer, France

Location

CHU Clémenceau

Caen, France

Location

Centre Henri Mondor

Créteil, France

Location

CHU de Grenoble

Grenoble, France

Location

Centre Le Mans

Le Mans, France

Location

Hôpital Saint Vincent de Paul

Lille, France

Location

CHRU de Limoges

Limoges, France

Location

Centre de Marseille

Marseille, France

Location

CHU Brabois

Nancy, France

Location

Centre de Nantes

Nantes, France

Location

Hopital Archet 1

Nice, France

Location

Centre Hospitalier Universitaire de Nimes

Nîmes, France

Location

Centre de St Louis, Hôpital St Louis

Paris, France

Location

Centre Hospitalier de la Région d'Annecy

Pringy, France

Location

Centre de Rouen, Centre Henri Becquerel

Rouen, France

Location

CHU Purpan

Toulouse, France

Location

CHU de Bretonneau

Tours, France

Location

Heinrich-Heine-Universität Düsseldorf

Düsseldorf, Germany

Location

Universitätsmedizin Mannheim

Mannheim, Germany

Location

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

Alessandria, AL, Italy

Location

Ospedale Riuniti

Ancona, AN, Italy

Location

Ospedale Cardinal Massaia

Asti, AT, Italy

Location

A.O. S. Giovanni Moscati

Avellino, AV, Italy

Location

Policlinico Università di Bari

Bari, BA, Italy

Location

Ospedale A. Perrino

Brindisi, BR, Italy

Location

Ospedale "Roberto Binaghi"

Cagliari, CA, Italy

Location

Ospedale L'Annunziata

Cosenza, CS, Italy

Location

Ospedale Ferrarotto

Catania, CT, Italy

Location

Ospedale Garibaldi

Catania, CT, Italy

Location

Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, FG, Italy

Location

Azienda Ospedaliera Universitaria Careggi

Florence, FI, Italy

Location

Università degli Studi di Genova

Genova, GE, Italy

Location

Ospedale Vito Fazzi

Lecce, LE, Italy

Location

IRCCS Ospedale Maggiore Policlinico

Milan, MI, Italy

Location

Ospedale Niguarda

Milan, MI, Italy

Location

Ospedale Civile Spirito Santo

Pescara, PE, Italy

Location

Azienda Ospedaliera Bianchi-Melacrino-Morelli

Reggio Calabria, RC, 89100, Italy

Location

Arcispedale di Santa Maria Nuova

Reggio Emilia, RE, Italy

Location

A.O. San Camillo Forlanini

Roma, RM, Italy

Location

Ospedale Sant'Eugenio

Roma, RM, Italy

Location

Policlinico Agostino Gemelli

Roma, RM, Italy

Location

Università Campus Bio Medico di Roma

Roma, RM, Italy

Location

Azienda Ospedaliera Sant'Andrea

Rome, RM, Italy

Location

IRCCS Istituto Regina Elena

Rome, RM, Italy

Location

Ospedale Nuova Regina Margherita

Rome, RM, Italy

Location

Policlinico Umberto I

Rome, RM, Italy

Location

Policlinico Universitario Tor Vergata

Rome, RM, Italy

Location

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

Salerno, SA, Italy

Location

Policlinico Santa Maria alle Scotte

Siena, SI, Italy

Location

A.O. Santa Maria

Terni, TE, Italy

Location

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

Torino, TO, Italy

Location

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

Torino, TO, Italy

Location

General Hospital Celje

Celje, Slovenia

Location

Univerzitetni klinini center Ljubljana

Ljubljana, Slovenia

Location

University Medical Centre Maribor

Maribor, Slovenia

Location

General Hospital Murska Sobota

Murska Sobota, Slovenia

Location

General Hospital Nova Gorica

Nova Gorica, Slovenia

Location

General Hospital Novo mesto

Novo Mesto, Slovenia

Location

General Hospital Slovenj Gradec

Slovenj Gradec, Slovenia

Location

Related Publications (1)

• 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.

  PMID: 37294914 DERIVED

MeSH Terms

Conditions

Myelodysplastic Syndromes; Thrombocytopenia

Interventions

eltrombopag

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Blood Platelet Disorders; Cytopenia

Study Officials

• Esther Natalie Oliva

  QOL-ONE Associazione Culturale e di Ricerca

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2016
• First Posted: September 23, 2016
• Study Start: June 11, 2011
• Primary Completion: February 2, 2017
• Study Completion (Estimated): October 1, 2026
• Last Updated: January 28, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (22); IT (33); DE (2); SL (7)