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

Primary Purpose

Myelodysplastic Syndromes

Status
Recruiting
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
Eltrombopag
Placebo
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myelodysplastic Syndromes focused on measuring Phase II, eltrombopag, ETB115, lower-risk MDS patients with platelet transfusion dependence, TPO-RA, placebo, myelodysplastic syndromes (MDS), platelet transfusion dependence

Eligibility Criteria

20 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Eltrombopag Arm

Placebo Arm

Arm Description

Participants randomized to a 1: 1 ratio will take eltrombopag.

Participants randomized to a 1: 1 ratio will take Placebo.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
Percentage of participants with platelet response (Hematologic improvement (HI) - platelet))
Platelet response is defined as HI-platelet per International Working Group criteria.
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.
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.
Percentage of hematologic improvement-erythroid and -neutrophil
per modified IWG criteria at 24 weeks, Year 1 and 2
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.
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.
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.
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.
Clinically significant bleeding events
This is defined as ≥ grade 2 events as per WHO bleeding scale.
Overall survival (OS)
OS is defined as time from randomization to death due to any cause.
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.
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.
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.
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.
Trough concentrations of eltrombopag at steady state
at each dose level in all the participants

Full Information

First Posted
March 4, 2021
Last Updated
October 17, 2023
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT04797000
Brief Title
Study of Efficacy and Safety of Eltrombopag in Lower-risk MDS Patients With Platelet Transfusion Dependence
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 25, 2021 (Actual)
Primary Completion Date
January 15, 2026 (Anticipated)
Study Completion Date
August 31, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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).
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelodysplastic Syndromes
Keywords
Phase II, eltrombopag, ETB115, lower-risk MDS patients with platelet transfusion dependence, TPO-RA, placebo, myelodysplastic syndromes (MDS), platelet transfusion dependence

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Participants, investigators, site staffs and site monitors will remain blinded to the identity of the treatment from the time of randomization until database lock for final analysis, and the clinical study team members and anyone involved in the Japan registration activities will be blinded until database lock for the primary analysis. Randomization data are kept strictly confidential until the time of unblinding and will not be accessible by anyone else involved in the study with the following exceptions: DMC members and who will perform data analysis for DMC.
Allocation
Randomized
Enrollment
36 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Eltrombopag Arm
Arm Type
Experimental
Arm Description
Participants randomized to a 1: 1 ratio will take eltrombopag.
Arm Title
Placebo Arm
Arm Type
Placebo Comparator
Arm Description
Participants randomized to a 1: 1 ratio will take Placebo.
Intervention Type
Drug
Intervention Name(s)
Eltrombopag
Other Intervention Name(s)
ETB115
Intervention Description
Eltrombopag comes in 12.5 mg & 25 mg tablets and is taken orally once per day (QD)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo comes in 12.5 mg & 25 mg tablets and is taken orally once per day (QD)
Primary Outcome Measure Information:
Title
Percentage of participants who achieve platelet transfusion independence at Week 24
Description
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.
Time Frame
Week 24
Secondary Outcome Measure Information:
Title
Time to platelet transfusion independence
Description
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.
Time Frame
Year 1, Year 2
Title
Duration of platelet transfusion independence
Description
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.
Time Frame
Year 1, Year 2
Title
Percentage of participants with platelet transfusion independence
Description
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.
Time Frame
Year 1, Year 2
Title
Percentage of participants with platelet transfusion frequency reduction at Week 24
Description
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.
Time Frame
Week 24
Title
Percentage of participants with platelet response (Hematologic improvement (HI) - platelet))
Description
Platelet response is defined as HI-platelet per International Working Group criteria.
Time Frame
Week 24, Year 1, Year 2
Title
Time to platelet response
Description
This is defined as time from the date of randomization to the first date of achieving the platelet response criteria per modified IWG criteria.
Time Frame
Week 24, Year 1, Year 2
Title
Duration of platelet response
Description
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.
Time Frame
Week 24, Year 1, Year 2
Title
Percentage of hematologic improvement-erythroid and -neutrophil
Description
per modified IWG criteria at 24 weeks, Year 1 and 2
Time Frame
Week 24, Year 1, Year 2
Title
Percentage of participants with disease progression excluding relapse after HI
Description
This is with regards to blast counts for both investigator assessment and central review per modified IWG criteria.
Time Frame
Week 24, Year 1, Year 2
Title
Percentage of participants with relapse after HI and transfusion independence
Description
The percentage of participants with relapse after HI and transfusion independence at Week 24, Year 1 and 2.
Time Frame
Week 24, Year 1, Year 2
Title
Percentage of participants with progression to Acute myeloid leukemia (AML)
Description
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.
Time Frame
Week 24, Year 1, Year 2
Title
Leukemia free survival (LFS)
Description
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.
Time Frame
Week 24, Year 1, Year 2
Title
Clinically significant bleeding events
Description
This is defined as ≥ grade 2 events as per WHO bleeding scale.
Time Frame
Week 24, Year 1, Year 2
Title
Overall survival (OS)
Description
OS is defined as time from randomization to death due to any cause.
Time Frame
Week 24, Year 1, Year 2
Title
Quality of Life measured using QLQ-C30
Description
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.
Time Frame
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.
Title
Pharmacokinetics (PK): Cmax
Description
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.
Time Frame
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.
Title
PK: Tmax
Description
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.
Time Frame
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.
Title
PK: AUC
Description
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.
Time Frame
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.
Title
Trough concentrations of eltrombopag at steady state
Description
at each dose level in all the participants
Time Frame
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Pharmaceuticals
Phone
+81337978748
Email
novartis.email@novartis.com
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Pharmaceuticals
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Narita
State/Province
Chiba
ZIP/Postal Code
286-8523
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Kitakyushu
State/Province
Fukuoka
ZIP/Postal Code
802-8533
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Kurume-city
State/Province
Fukuoka
ZIP/Postal Code
830-8543
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Fukushima city
State/Province
Fukushima
ZIP/Postal Code
960 1295
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Gifu shi
State/Province
Gifu
ZIP/Postal Code
500 8513
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Ohtake
State/Province
Hiroshima
ZIP/Postal Code
739-0696
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Nishinomiya
State/Province
Hyogo
ZIP/Postal Code
663 8501
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Mito
State/Province
Ibaraki
ZIP/Postal Code
310-0015
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Kanazawa
State/Province
Ishikawa
ZIP/Postal Code
920-0853
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Isehara
State/Province
Kanagawa
ZIP/Postal Code
259-1193
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Yokohama
State/Province
Kanagawa
ZIP/Postal Code
221-0855
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Kumamoto-city
State/Province
Kumamoto
ZIP/Postal Code
860-0008
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Sendai city
State/Province
Miyagi
ZIP/Postal Code
980 8574
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Matsumoto-city
State/Province
Nagano
ZIP/Postal Code
399-8701
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Nagasaki-city
State/Province
Nagasaki
ZIP/Postal Code
852-8501
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Osaka Sayama
State/Province
Osaka
ZIP/Postal Code
589 8511
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Hamamatsu
State/Province
Shizuoka
ZIP/Postal Code
432-8580
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Bunkyo-ku
State/Province
Tokyo
ZIP/Postal Code
113-8603
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Itabashi ku
State/Province
Tokyo
ZIP/Postal Code
173 8606
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Shimonoseki
State/Province
Yamaguchi
ZIP/Postal Code
750-0061
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Aomori
ZIP/Postal Code
030 8553
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Chiba
ZIP/Postal Code
260-0852
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Osaka
ZIP/Postal Code
534-0021
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Yamagata
ZIP/Postal Code
990 9585
Country
Japan
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
IPD Sharing URL
https://www.clinicalstudydatarequest.com

Learn more about this trial

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

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