Clinical trial NCT04797000: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Myelodysplastic Syndromes
Keywords: Phase II
eltrombopag
ETB115
lower-risk MDS patients with platelet transfusion dependence
TPO-RA
placebo
myelodysplastic syndromes (MDS)
platelet transfusion dependence
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2021-03-15
Enrollment: 36
Sex: ALL
Minimum age (years): 20
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Percentage of participants who achieve platelet transfusion independence at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Time to platelet transfusion independence
timeFrame: Year 1, Year 2
measure: Duration of platelet transfusion independence
timeFrame: Year 1, Year 2
measure: Percentage of participants with platelet transfusion independence
timeFrame: Year 1, Year 2
measure: Percentage of participants with platelet transfusion frequency reduction at Week 24
timeFrame: Week 24
measure: Percentage of participants with platelet response (Hematologic improvement (HI) - platelet))
timeFrame: Week 24, Year 1, Year 2
measure: Time to platelet response
timeFrame: Week 24, Year 1, Year 2
measure: Duration of platelet response
timeFrame: Week 24, Year 1, Year 2
measure: Percentage of hematologic improvement-erythroid and -neutrophil
timeFrame: Week 24, Year 1, Year 2
measure: Percentage of participants with disease progression excluding relapse after HI
timeFrame: Week 24, Year 1, Year 2
measure: Percentage of participants with relapse after HI and transfusion independence
timeFrame: Week 24, Year 1, Year 2
measure: Percentage of participants with progression to Acute myeloid leukemia (AML)
timeFrame: Week 24, Year 1, Year 2
measure: Leukemia free survival (LFS)
timeFrame: Week 24, Year 1, Year 2
measure: Clinically significant bleeding events
timeFrame: Week 24, Year 1, Year 2
measure: Overall survival (OS)
timeFrame: Week 24, Year 1, Year 2
measure: Quality of Life measured using QLQ-C30
timeFrame: 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.
measure: Pharmacokinetics (PK): Cmax
timeFrame: 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.
measure: PK: Tmax
timeFrame: 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.
measure: PK: AUC
timeFrame: 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.
measure: Trough concentrations of eltrombopag at steady state
timeFrame: 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.
Other outcomes:
Locations:
city: Narita
country: Japan
facility: Novartis Investigative Site
state: Chiba
city: Kurume-city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Fukushima city
country: Japan
facility: Novartis Investigative Site
state: Fukushima
city: Gifu shi
country: Japan
facility: Novartis Investigative Site
state: Gifu
city: Ohtake
country: Japan
facility: Novartis Investigative Site
state: Hiroshima
city: Nishinomiya
country: Japan
facility: Novartis Investigative Site
state: Hyogo
city: Mito
country: Japan
facility: Novartis Investigative Site
state: Ibaraki
city: Kanazawa
country: Japan
facility: Novartis Investigative Site
state: Ishikawa
city: Isehara
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Yokohama
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Sendai city
country: Japan
facility: Novartis Investigative Site
state: Miyagi
city: Matsumoto-city
country: Japan
facility: Novartis Investigative Site
state: Nagano
city: Nagasaki-city
country: Japan
facility: Novartis Investigative Site
state: Nagasaki
city: Osaka Sayama
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Bunkyo-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Itabashi ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Shimonoseki
country: Japan
facility: Novartis Investigative Site
state: Yamaguchi
city: Aomori
country: Japan
facility: Novartis Investigative Site
city: Chiba
country: Japan
facility: Novartis Investigative Site
city: Kumamoto
country: Japan
facility: Novartis Investigative Site
city: Osaka
country: Japan
facility: Novartis Investigative Site
city: Yamagata
country: Japan
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: