Eltrombopag for the treatment of thrombocytopenia due to low - and intermediate risk myelodysplastic syndromes.

Phase 2

Not yet recruiting

• Conditions: Myelodysplastic syndromes

• Registration Number: 2024-520133-72-00
• Lead Sponsor: Associazione Qol-One

Brief Summary

Phase 1

Primary Objectives

To evaluate the effect of treatment relative to placebo on:

1. response rate: the proportion of patients achieving a complete response (CR) or response (R) during the treatment period

2. safety and tolerability in terms of frequency of adverse events (AE) and serious adverse events (SAE).

Phase 2

Primary objectives

To evaluate the effect of treatment relative to placebo on:

1. duration of platelet response;

2. long-term safety and tolerability

Detailed Description

Not available

Study Timeline

• Study First Posted: 2025-02-05
• Last Update Posted: 2025-06-24

Recruitment & Eligibility

• Status: Authorised, recruitment pending
• Sex: Not specified
• Target Recruitment: 160

Inclusion Criteria

Adult subjects (18 years of age or older) with low or intermediate-1 IPSS risk MDS and stable disease.

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.

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 BM examination which includes cytomorphology and cytogenetics. Histopathology should be performed.

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 Performance Status 0-3.

Subject is able to understand and comply with protocol requirements and instructions.

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 by more than 20%.

Exclusion Criteria

MDS with intermediate-2 or high IPSS risk.

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).

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 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. 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Phase 1. Proportion of patients obtaining CR or R during the six month treatment period.		Phase 1. Proportion of patients obtaining CR or R during the six month treatment period.
Phase 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.		Phase 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.
Phase 2. Duration of platelet response.		Phase 2. Duration of platelet response.
Phase 1. Long-term safety and tolerability.		Phase 1. Long-term safety and tolerability.

Secondary Outcome Measures

Name	Time	Method
Changes in quality of life (QoL) scores.		Changes in quality of life (QoL) scores.
Frequency of platelet transfusions during the treatment and follow-up periods.		Frequency of platelet transfusions during the treatment and follow-up periods.
Duration of platelet transfusion independence.		Duration of platelet transfusion independence.
Difference in time to response (time from starting treatment to time of achievement of CR or R).		Difference in time to response (time from starting treatment to time of achievement of CR or R).
Duration of response during the treatment and follow-up periods.		Duration of response during the treatment and follow-up periods.
Incidence and severity of bleeding using the WHO Bleeding Scale.		Incidence and severity of bleeding using the WHO Bleeding Scale.
OS and LFS.		OS and LFS.
Eltrombopag population pharmacokinetic parameters and plasma concentration data. The relationship between eltrombopag pharmacokinetics and relevant safety and efficacy endpoints will be explored, as data permit.		Eltrombopag population pharmacokinetic parameters and plasma concentration data. The relationship between eltrombopag pharmacokinetics and relevant safety and efficacy endpoints will be explored, as data permit.
Phase 1 primary endpoints have been reached and have been publish (Lancet Haematol. 2017 Mar;4(3):e127-e136)		Phase 1 primary endpoints have been reached and have been publish (Lancet Haematol. 2017 Mar;4(3):e127-e136)

Trial Locations

Locations (9)

Ospedale S. Eugenio, ASL Roma 2; 🇮🇹 Roma, Italy

A.O.U Maggiore della Carità; 🇮🇹 Italy

AOU Policlinico Umberto I -Università degli studi di Roma "La Sapienza"; 🇮🇹 Rome, Italy

IRCSS Ospedale Policlinico San Martino; 🇮🇹 Genova, Italy

Grande Ospedale Metropolitano Bianchi Melacrino Morelli; 🇮🇹 Reggio Calabria, Italy

IFO-Regina Elena Institute for Cancer Research; 🇮🇹 Rome, Italy

Istituto Tumori Bari Giovanni Paolo II; 🇮🇹 Bari, Italy

Azienda Ospedaliera Universitaria Careggi; 🇮🇹 Firenze, Italy

ASST Grande Ospedale Metropolitano Niguarda; 🇮🇹 Milano, Italy

Ospedale S. Eugenio, ASL Roma 2

🇮🇹Roma, Italy

Pasquale Niscola

Site contact

0651001

pasquale.niscola@aslroma2.it