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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Associazione Qol-One

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

5 Feb 2025 → ongoing

Decision date (initial)

2025-02-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-520133-72-00

EudraCT number

2010-022890-33

ClinicalTrials.gov

NCT02912208

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Dose response, Safety, Therapy, Pharmacokinetic

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

Secondary objectives 8

1. To evaluate the effect of treatment relative to placebo on quality of life (QoL) scores;
2. To evaluate the effect of treatment relative to placebo on number of monthly platelet transfusions
3. To evaluate the effect of treatment relative to placebo on duration of transfusion independence
4. To evaluate the effect of treatment relative to placebo on time to response (time from starting treatment to time of achievement of CR or PR) as measured by the MDS response criteria
5. To evaluate the effect of treatment relative to placebo on incidence and severity of bleeding using the WHO Bleeding Scale
6. To evaluate the effect of treatment relative to placebo on overall survival (OS) at 2 and at 5 years
7. To evaluate the effect of treatment relative to placebo on leukemia-free survival (LFS) at 2 and at 5 years(events for LFS are defined as death and progression to AML
8. To evaluate eltrombopag population pharmacokinetics

Conditions and MedDRA coding

Myelodysplastic syndromes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

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 BM examination which includes cytomorphology and cytogenetics. Histopathology should be performed.
6. 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.
7. ECOG Performance Status 0-3.
8. Subject is able to understand and comply with protocol requirements and instructions.
9. 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%.
10. 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 12

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 TPO-R agonists.
4. 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)
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).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

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

Secondary endpoints 9

1. Changes in quality of life (QoL) scores.
2. Frequency of platelet transfusions during the treatment and follow-up periods.
3. Duration of platelet transfusion independence.
4. Difference in time to response (time from starting treatment to time of achievement of CR or R).
5. Duration of response during the treatment and follow-up periods.
6. Incidence and severity of bleeding using the WHO Bleeding Scale.
7. OS and LFS.
8. 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.
9. Phase 1 primary endpoints have been reached and have been publish (Lancet Haematol. 2017 Mar;4(3):e127-e136)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Associazione Qol-One

Sponsor organisation

Associazione Qol-One

Address

Via Carro E Quattrone 8

City

Reggio Calabria

Postcode

89134

Country

Italy

Scientific contact point

Organisation

Associazione Qol-One

Contact name

Esther Natalie Oliva

Public contact point

Organisation

Associazione Qol-One

Contact name

Roberta Siclari

Locations

1 EU/EEA country · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications