Description:
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).
Title
- 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
Clinical Trial IDs
- ORG STUDY ID:
CETB115L11201
- NCT ID:
NCT04797000
Conditions
- Myelodysplastic Syndromes
Interventions
| Drug | Synonyms | Arms |
|---|
| Eltrombopag | ETB115 | Eltrombopag Arm |
| Placebo | | Placebo Arm |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Eltrombopag Arm | Experimental | Participants randomized to a 1: 1 ratio will take eltrombopag. | |
| Placebo Arm | Placebo Comparator | Participants randomized to a 1: 1 ratio will take Placebo. | |
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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 20 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Percentage of participants who achieve platelet transfusion independence at Week 24 |
| Time Frame: | Week 24 |
| Safety Issue: | |
| 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. |
Secondary Outcome Measures
| Measure: | Time to platelet transfusion independence |
| Time Frame: | Year 1, Year 2 |
| Safety Issue: | |
| 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. |
| Measure: | Duration of platelet transfusion independence |
| Time Frame: | Year 1, Year 2 |
| Safety Issue: | |
| 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. |
| Measure: | Percentage of participants with platelet transfusion independence |
| Time Frame: | Year 1, Year 2 |
| Safety Issue: | |
| 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. |
| Measure: | Percentage of participants with platelet transfusion frequency reduction at Week 24 |
| Time Frame: | Week 24 |
| Safety Issue: | |
| 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. |
| Measure: | Percentage of participants with platelet response (Hematologic improvement (HI) - platelet)) |
| Time Frame: | Week 24, Year 1, Year 2 |
| Safety Issue: | |
| Description: | Platelet response is defined as HI-platelet per International Working Group criteria. |
| Measure: | Time to platelet response |
| Time Frame: | Week 24, Year 1, Year 2 |
| Safety Issue: | |
| 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. |
| Measure: | Duration of platelet response |
| Time Frame: | Week 24, Year 1, Year 2 |
| Safety Issue: | |
| 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. |
| Measure: | Percentage of hematologic improvement-erythroid and -neutrophil |
| Time Frame: | Week 24, Year 1, Year 2 |
| Safety Issue: | |
| Description: | per modified IWG criteria at 24 weeks, Year 1 and 2 |
| Measure: | Percentage of participants with disease progression excluding relapse after HI |
| Time Frame: | Week 24, Year 1, Year 2 |
| Safety Issue: | |
| Description: | This is with regards to blast counts for both investigator assessment and central review per modified IWG criteria. |
| Measure: | Percentage of participants with relapse after HI and transfusion independence |
| Time Frame: | Week 24, Year 1, Year 2 |
| Safety Issue: | |
| Description: | The percentage of participants with relapse after HI and transfusion independence at Week 24, Year 1 and 2. |
| Measure: | Percentage of participants with progression to Acute myeloid leukemia (AML) |
| Time Frame: | Week 24, Year 1, Year 2 |
| Safety Issue: | |
| 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. |
| Measure: | Leukemia free survival (LFS) |
| Time Frame: | Week 24, Year 1, Year 2 |
| Safety Issue: | |
| 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. |
| Measure: | Clinically significant bleeding events |
| Time Frame: | Week 24, Year 1, Year 2 |
| Safety Issue: | |
| Description: | This is defined as ≥ grade 2 events as per WHO bleeding scale. |
| Measure: | Overall survival (OS) |
| Time Frame: | Week 24, Year 1, Year 2 |
| Safety Issue: | |
| Description: | OS is defined as time from randomization to death due to any cause. |
| Measure: | Quality of Life measured using QLQ-C30 |
| 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. |
| Safety Issue: | |
| 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. |
| Measure: | Pharmacokinetics (PK): Cmax |
| 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. |
| Safety Issue: | |
| 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. |
| Measure: | PK: Tmax |
| 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. |
| Safety Issue: | |
| 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. |
| Measure: | PK: AUC |
| 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. |
| Safety Issue: | |
| 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. |
| Measure: | Trough concentrations of eltrombopag at steady state |
| 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. |
| Safety Issue: | |
| Description: | at each dose level in all the participants |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Novartis Pharmaceuticals |
Trial Keywords
- Phase II
- eltrombopag
- ETB115
- lower-risk MDS patients with platelet transfusion dependence
- TPO-RA
- placebo
- myelodysplastic syndromes (MDS)
- platelet transfusion dependence
Last Updated
June 2, 2021
