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

Sponsor

Associazione Qol-one (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02912208

Collaborator

(none)

174

Enrollment

Locations

Arms

183.7

Anticipated Duration (Months)

2.7

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndromes Thrombocytopenia	Drug: Eltrombopag/Revolade Other: Placebo	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

174 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Treatment

Official Title:

Eltrombopag for the Treatment of Thrombocytopenia Due to Low- and Intermediate Risk Myelodysplastic Syndromes (EQoL-MDS)

Actual Study Start Date :

Jun 11, 2011

Actual Primary Completion Date :

Feb 2, 2017

Anticipated Study Completion Date :

Oct 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1 (Eltrombopag) Arm 1 is the active treatment arm	Drug: 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).
Placebo Comparator: Arm 2 (Placebo) Arm 2 is the control arm	Other: Placebo The administration is the same of eltrombopag

Arm

Intervention/Treatment

Experimental: Arm 1 (Eltrombopag)

Arm 1 is the active treatment arm

Drug: 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).

Placebo Comparator: Arm 2 (Placebo)

Arm 2 is the control arm

Other: Placebo

The administration is the same of eltrombopag

Outcome Measures

Primary Outcome Measures

Response rate [Six months]
Proportion of patients achieving a complete response (CR) or response (R) during the treatment period
Safety and Tolerability (number of adverse events) [Six month]
Safety and tolerability in terms of frequency of adverse events (AE) and serious adverse events (SAE)
Duration of platelet response [five years]
long-term safety and tolerability (number adverse events in the long term) [five years]
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

Secondary Outcome Measures

Quality of life (QoL) score [six months]
to evaluate the changes of the quality of life in the two arms
number of monthly platelet transfusions [six months]
duration of transfusion independence [six months]
time to response [six months]
time to response (time from starting treatment to time of achievement of CR or PR)
incidence and severity of bleeding [six months]
incidence and severity of bleeding using the WHO (World Health Organization)Bleeding Scale
overall survival [2 and 5 years]
overall survival (OS) at 2 and at 5 years
leukemia-free survival (LFS) [2 and 5 years]
leukemia-free survival (LFS) at 2 and at 5 years (events for LFS are defined as death and progression to AML);

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CHU Amiens	Amiens		France
2	Centre d'Avignon	Avignon		France
3	Hôpital de la Côte Basque	Bayonne		France
4	Centre d'Avicenne, Hôpital d'Avicenne	Bobigny		France
5	CHU de Haut-Lévèque	Bordeaux		France
6	Centre Hospitalier de Boulogne Sur Mer	Boulogne Sur Mer		France
7	CHU Clémenceau	Caen		France
8	Centre Henri Mondor	Creteil		France
9	CHU de Grenoble	Grenoble		France
10	Centre Le Mans	Le Mans		France
11	Hôpital Saint Vincent de Paul	Lille		France
12	CHRU de Limoges	Limoges		France
13	Centre de Marseille	Marseille		France
14	CHU Brabois	Nancy		France
15	Centre de Nantes	Nantes		France
16	Hopital Archet 1	Nice		France
17	Centre Hospitalier Universitaire de Nimes	Nimes		France
18	Centre de St Louis, Hôpital St Louis	Paris		France
19	Centre Hospitalier de la Région d'Annecy	Pringy		France
20	Centre de Rouen, Centre Henri Becquerel	Rouen		France
21	CHU Purpan	Toulouse		France
22	CHU de Bretonneau	Tours		France
23	Heinrich-Heine-Universität Düsseldorf	Düsseldorf		Germany
24	Universitätsmedizin Mannheim	Mannheim		Germany
25	A.O. SS. Antonio e Biagio e Cesare Arrigo	Alessandria	AL	Italy
26	Ospedale Riuniti	Ancona	AN	Italy
27	Ospedale Cardinal Massaia	Asti	AT	Italy
28	A.O. S. Giovanni Moscati	Avellino	AV	Italy
29	Policlinico Università di Bari	Bari	BA	Italy
30	Ospedale A. Perrino	Brindisi	BR	Italy
31	Ospedale "Roberto Binaghi"	Cagliari	CA	Italy
32	Ospedale L'Annunziata	Cosenza	CS	Italy
33	Ospedale Ferrarotto	Catania	CT	Italy
34	Ospedale Garibaldi	Catania	CT	Italy
35	Ospedale Casa Sollievo della Sofferenza	San Giovanni Rotondo	FG	Italy
36	Azienda Ospedaliera Universitaria Careggi	Firenze	FI	Italy
37	Università degli Studi di Genova	Genova	GE	Italy
38	Ospedale Vito Fazzi	Lecce	LE	Italy
39	IRCCS Ospedale Maggiore Policlinico	Milano	MI	Italy
40	Ospedale Niguarda	Milano	MI	Italy
41	Ospedale Civile Spirito Santo	Pescara	PE	Italy
42	Azienda Ospedaliera Bianchi-Melacrino-Morelli	Reggio Calabria	RC	Italy	89100
43	Arcispedale di Santa Maria Nuova	Reggio Emilia	RE	Italy
44	A.O. San Camillo Forlanini	Roma	RM	Italy
45	Ospedale Sant'Eugenio	Roma	RM	Italy
46	Policlinico Agostino Gemelli	Roma	RM	Italy
47	Università Campus Bio Medico di Roma	Roma	RM	Italy
48	Azienda Ospedaliera Sant'Andrea	Rome	RM	Italy
49	IRCCS Istituto Regina Elena	Rome	RM	Italy
50	Ospedale Nuova Regina Margherita	Rome	RM	Italy
51	Policlinico Umberto I	Rome	RM	Italy
52	Policlinico Universitario Tor Vergata	Rome	RM	Italy
53	A.O.U. San Giovanni di Dio e Ruggì D'Aragona	Salerno	SA	Italy
54	Policlinico Santa Maria alle Scotte	Siena	SI	Italy
55	A.O. Santa Maria	Terni	TE	Italy
56	A.O. Citta' della Salute e della Scienza di Torino	Torino	TO	Italy
57	U.O. Citta' della Salute e della Scienza di Torino	Torino	TO	Italy
58	General Hospital Celje	Celje		Slovenia
59	Univerzitetni klinini center Ljubljana	Ljubljana		Slovenia
60	University Medical Centre Maribor	Maribor		Slovenia
61	General Hospital Murska Sobota	Murska Sobota		Slovenia
62	General Hospital Nova Gorica	Nova Gorica		Slovenia
63	General Hospital Novo mesto	Novo Mesto		Slovenia
64	General Hospital Slovenj Gradec	Slovenj Gradec		Slovenia

Sponsors and Collaborators

Associazione Qol-one

Investigators

Study Chair: Esther Natalie Oliva, QOL-ONE Associazione Culturale e di Ricerca

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Associazione Qol-one

ClinicalTrials.gov Identifier:

NCT02912208

Other Study ID Numbers:

EQoL-MDS

First Posted:

Sep 23, 2016

Last Update Posted:

Jan 28, 2022

Last Verified:

Jan 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Additional relevant MeSH terms:

Preleukemia

Myelodysplastic Syndromes

Thrombocytopenia

Syndrome

Study Results

No Results Posted as of Jan 28, 2022