Study of Efficacy and Safety of Eltrombopag in Lower-risk MDS Patients With Platelet Transfusion Dependence

Myelodysplastic Syndromes Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled, Japan Local Phase II Clinical Study Comparing Eltrombopag Monotherapy Versus Placebo in Adult Lower-risk Myelodysplastic Syndromes (MDS) Patients With Platelet Transfusion Dependence

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04797000
• Other study ID #: CETB115L11201
• Status: Recruiting
• Phase: Phase 2
• Start date: May 25, 2021
• Est. completion date: August 31, 2027

Study information

• Verified date: October 2023
• Source: Novartis
• Contact: Novartis Pharmaceuticals
• Phone: +81337978748
• Email: novartis.email[@]novartis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is designed to evaluate the efficacy and safety of eltrombopag monotherapy in Japanese adult patients with platelet transfusion-dependent lower-risk Myelodysplastic syndromes (LR-MDS).

Description:

This is a randomized, double-blind, placebo-controlled, Japanese local phase II study to evaluate the efficacy and safety of eltrombopag monotherapy in Japanese adult patients with platelet transfusion-dependent lower-risk MDS (IPSS-R very low, low, intermediate risk with bone marrow blast count < 5% and cytogenetic very good, good or intermediate risk). Platelet transfusion dependence at baseline is defined as receiving platelet transfusion regularly with a frequency of 2 or more times within 4 weeks prior to randomization. Platelet transfusion should be performed for a patient with platelet counts < 20 X 10^9/L, or with hemorrhagic symptoms and platelet counts < 30 X 10^9/L.

The primary objective is to demonstrate superiority of eltrombopag versus placebo in terms of the proportion of participants who achieve platelet transfusion independence at Week 24.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: August 31, 2027
• Est. primary completion date: January 15, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 99 Years

Eligibility

Inclusion Criteria:

• Patients diagnosed with MDS according to the WHO classification revised 4th edition by investigator assessment with one of the following prognostic risk categories, based on the International

Prognostic Scoring System (IPSS-R):

• very low (0-1.5)

• low (2-3)

• intermediate risks (3.5-4.5) All following criteria for prognostic variables per IPSS-R should be met.

• Bone marrow blast < 5% (per both investigator's assessment and central review)

• Cytogenetic very good, good or intermediate risk corresponding to IPSS-R

• Platelet transfusion dependence

• Refractory, intolerant to, or ineligible for MDS treatments

• Eastern Cooperative Oncology Group (ECOG) Performance status (PS) 0 or 1

Exclusion Criteria:

• Patients with a history of prior administration of eltrombopag, romiplostim, or other TPO-RA

• Therapy-related MDS per WHO classification revised 4th edition

• MDS/myeloproliferative neoplasms including chronic myelomonocytic leukaemia per the WHO classification revised 4th edition

• MDS with excess blasts (EB) per WHO classification revised 4th edition

• Known history of IPSS-R high or very high risk MDS

• Currently receiving treatments for MDS (e.g., HMA, cyclosporine A (CsA) or lenalidomide). Supportive treatment with erythropoiesis-stimulating agents (ESAs) in anemic patients or granulocyte-colony stimulating factor (G-CSF) in patients with severe neutropenia and recurrent infections is allowed if at stable dosage for 3 months prior to screening and continued at the same dosing/schedule until the optimal dose of eltrombopag has been established.

• Patients scheduled for hematopoietic stem cell transplantation

• Bone marrow fibrosis that leads to an inability to aspirate adequate bone marrow sample

• Known thrombophilic risk factors (except in cases where potential benefits of participating in the study outweighed potential risks of thromboembolic events(TEE), as determined by the investigator)

Other protocol-defined inclusion/exclusion criteria may apply.

Related Conditions & MeSH terms

• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• Eltrombopag
Eltrombopag comes in 12.5 mg & 25 mg tablets and is taken orally once per day (QD)
• Placebo
Placebo comes in 12.5 mg & 25 mg tablets and is taken orally once per day (QD)

Locations

Country	Name	City	State
Japan	Novartis Investigative Site	Aomori
Japan	Novartis Investigative Site	Bunkyo-ku	Tokyo
Japan	Novartis Investigative Site	Chiba
Japan	Novartis Investigative Site	Fukushima city	Fukushima
Japan	Novartis Investigative Site	Gifu shi	Gifu
Japan	Novartis Investigative Site	Hamamatsu	Shizuoka
Japan	Novartis Investigative Site	Isehara	Kanagawa
Japan	Novartis Investigative Site	Itabashi ku	Tokyo
Japan	Novartis Investigative Site	Kanazawa	Ishikawa
Japan	Novartis Investigative Site	Kitakyushu	Fukuoka
Japan	Novartis Investigative Site	Kumamoto-city	Kumamoto
Japan	Novartis Investigative Site	Kurume-city	Fukuoka
Japan	Novartis Investigative Site	Matsumoto-city	Nagano
Japan	Novartis Investigative Site	Mito	Ibaraki
Japan	Novartis Investigative Site	Nagasaki-city	Nagasaki
Japan	Novartis Investigative Site	Narita	Chiba
Japan	Novartis Investigative Site	Nishinomiya	Hyogo
Japan	Novartis Investigative Site	Ohtake	Hiroshima
Japan	Novartis Investigative Site	Osaka
Japan	Novartis Investigative Site	Osaka Sayama	Osaka
Japan	Novartis Investigative Site	Sendai city	Miyagi
Japan	Novartis Investigative Site	Shimonoseki	Yamaguchi
Japan	Novartis Investigative Site	Yamagata
Japan	Novartis Investigative Site	Yokohama	Kanagawa

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of participants who achieve platelet transfusion independence at Week 24	Platelet transfusion independence is defined as the absence of platelet transfusion for at least 8 weeks. Platelet count should be higher than the baseline count.	Week 24
Secondary	Time to platelet transfusion independence	This is defined as time from the date of randomization to the first day of a platelet transfusion-free period lasting at least 8 weeks.	Year 1, Year 2
Secondary	Duration of platelet transfusion independence	This is defined for participants who have achieved platelet transfusion independence only and will be calculated from the first date of platelet transfusion-free resulting in achievement of transfusion independence to the date before becoming platelet transfusion dependent.	Year 1, Year 2
Secondary	Percentage of participants with platelet transfusion independence	Platelet transfusion independence is defined as the absence of platelet transfusion for at least 8 weeks. Platelet count should be higher than the baseline count.	Year 1, Year 2
Secondary	Percentage of participants with platelet transfusion frequency reduction at Week 24	This is defined as a reduction by at least 50 percent during the 4 prior weeks as compared to the 4 weeks prior to randomization.	Week 24
Secondary	Percentage of participants with platelet response (Hematologic improvement (HI) - platelet))	Platelet response is defined as HI-platelet per International Working Group criteria.	Week 24, Year 1, Year 2
Secondary	Time to platelet response	This is defined as time from the date of randomization to the first date of achieving the platelet response criteria per modified IWG criteria.	Week 24, Year 1, Year 2
Secondary	Duration of platelet response	This is defined for participants who have achieved platelet response and will be calculated from the first date of achieving the platelet response criteria to the date before loss of platelet response per modified IWG criteria.	Week 24, Year 1, Year 2
Secondary	Percentage of hematologic improvement-erythroid and -neutrophil	per modified IWG criteria at 24 weeks, Year 1 and 2	Week 24, Year 1, Year 2
Secondary	Percentage of participants with disease progression excluding relapse after HI	This is with regards to blast counts for both investigator assessment and central review per modified IWG criteria.	Week 24, Year 1, Year 2
Secondary	Percentage of participants with relapse after HI and transfusion independence	The percentage of participants with relapse after HI and transfusion independence at Week 24, Year 1 and 2.	Week 24, Year 1, Year 2
Secondary	Percentage of participants with progression to Acute myeloid leukemia (AML)	This is defined as = 20% blasts at Week 24, Year 1 and 2 for both investigator assessment and central review per WHO classification revised 4th edition.	Week 24, Year 1, Year 2
Secondary	Leukemia free survival (LFS)	This is defined as time from the date of randomization to progression to AML per WHO classification revised 4th edition of = 20 percent blasts or death due to any cause for both investigator assessment and central review.	Week 24, Year 1, Year 2
Secondary	Clinically significant bleeding events	This is defined as = grade 2 events as per WHO bleeding scale.	Week 24, Year 1, Year 2
Secondary	Overall survival (OS)	OS is defined as time from randomization to death due to any cause.	Week 24, Year 1, Year 2
Secondary	Quality of Life measured using QLQ-C30	The changes from baseline to each visit where measured using QLQ-C30. EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Subject's responses to 28 questions about their physical functioning, disease symptoms, global health status and utilities are scored on a 4-point scale (1=Not at all to 4=Very much), a low score indicates a high / healthy level of functioning. And the responses to 2 questions about health-related QoL are scored on a 7-point scale (1=Very poor to 7=Excellent), a high score indicates a high / healthy level of functioning.; Using linear transformation, raw scores are standardized, so that scores range from 0 to 100.	Baseline, every 4 weeks until week 52, every 8 weeks after week 52 up to end of treatment or end of post-treatment follow-up, approximately 3.5 years.
Secondary	Pharmacokinetics (PK): Cmax	Full PK profile of eltrombopag over 24 hours at steady state at the initial dose, and at 125 mg and 150 mg when applicable, in subset of participants.	Intensive: pre-dose, 1, 2, 4, 6, 8, and 24 hours post-dose. Trough: 15th days after starting the initial dose or each dose modification until reaching the maximum dose.
Secondary	PK: Tmax	Full PK profile of eltrombopag over 24 hours at steady state at the initial dose, and at 125 mg and 150 mg when applicable, in subset of participants.	Intensive: pre-dose, 1, 2, 4, 6, 8, and 24 hours post-dose. Trough: 15th days after starting the initial dose or each dose modification until reaching the maximum dose.
Secondary	PK: AUC	Full PK profile of eltrombopag over 24 hours at steady state at the initial dose, and at 125 mg and 150 mg when applicable, in subset of participants.	Intensive: pre-dose, 1, 2, 4, 6, 8, and 24 hours post-dose. Trough: 15th days after starting the initial dose or each dose modification until reaching the maximum dose.
Secondary	Trough concentrations of eltrombopag at steady state	at each dose level in all the participants	Intensive: pre-dose, 1, 2, 4, 6, 8, and 24 hours post-dose. Trough: 15th days after starting the initial dose or each dose modification until reaching the maximum dose.