Эта страница была переведена автоматически, точность перевода не гарантируется. Пожалуйста, обратитесь к английской версии для исходного текста.

A Study of Eltrombopag or Placebo in Combination With Azacitidine in Subjects With International Prognostic Scoring System (IPSS) Intermediate-1, Intermediate-2 or High-risk Myelodysplastic Syndromes (MDS)

12 ноября 2017 г. обновлено: Novartis Pharmaceuticals

A Randomized, Double-blind, Placebo-controlled, Phase III, Multi-centre Study of Eltrombopag or Placebo in Combination With Azacitidine in Subjects With IPSS Intermediate-1, Intermediate 2 and High-risk Myelodysplastic Syndromes (MDS) SUPPORT: A StUdy of eltromboPag in myelodysPlastic SyndrOmes Receiving azaciTidine

Eltrombopag olamine (SB-497115-GR) is an orally bioavailable, small molecule thrombopoietin receptor agonist that may be beneficial in medical disorders associated with thrombocytopenia. Eltrombopag has been shown to increase platelet counts in patients with thrombocytopenia from various etiologies (Idiopathic thrombocytopenic purpura [ITP], liver disease, aplastic anemia and chemotherapy induced thrombocytopenia). Approximately 350 subjects will be randomized in a 1:1 ratio (175 into the eltrombopag arm and 175 into the placebo arm). Approximately 55 subjects will be enrolled into the azacitidine. Subjects with intermediate-1, intermediate-2 or high risk MDS by IPSS, and baseline platelet count of <75 Giga (10^9) per liter (Gi/L) will only be enrolled. This is a randomized, double-blind, parallel group, placebo-controlled study designed to explore the platelet supportive care effects of eltrombopag versus placebo in combination with the standard of care hypomethylating agent, azacitidine. The primary objective of this study is to determine the effect of eltrombopag versus placebo on the proportion of subjects who are platelet transfusion free during the first 4 cycles of azacitidine therapy. Key secondary endpoints include overall survival, disease response, and disease progression.

Обзор исследования

Статус

Прекращено

Условия

Вмешательство/лечение

Тип исследования

Интервенционный

Регистрация (Действительный)

356

Фаза

  • Фаза 3

Контакты и местонахождение

В этом разделе приведены контактные данные лиц, проводящих исследование, и информация о том, где проводится это исследование.

Места учебы

  • Австралия
    • New South Wales
      • Kogarah, New South Wales, Австралия, 2217
        • Novartis Investigative Site
    • South Australia
      • Adelaide, South Australia, Австралия, 5000
        • Novartis Investigative Site
    • Victoria
      • Clayton, Victoria, Австралия, 3168
        • Novartis Investigative Site
      • East Melbourne, Victoria, Австралия, 3002
        • Novartis Investigative Site
      • Melbourne, Victoria, Австралия, 3000
        • Novartis Investigative Site
  • Австрия
      • Graz, Австрия, 8036
        • Novartis Investigative Site
      • Innsbruck, Австрия, A-6020
        • Novartis Investigative Site
      • Linz, Австрия, 4020
        • Novartis Investigative Site
      • Rankweil, Австрия, A-6830
        • Novartis Investigative Site
      • Salzburg, Австрия, A-5020
        • Novartis Investigative Site
      • Steyr, Австрия, 4400
        • Novartis Investigative Site
      • Vienna, Австрия, 1140
        • Novartis Investigative Site
  • Аргентина
      • Ciudad Autonoma de Buenos Aires, Аргентина, 1114
        • Novartis Investigative Site
      • Ciudad Autonoma de Buenos Aires, Аргентина, 1425
        • Novartis Investigative Site
      • Ciudad Autonoma de Buenos Aires, Аргентина, C1181ACH
        • Novartis Investigative Site
      • Santa Fe, Аргентина, S3000ADL
        • Novartis Investigative Site
  • Бельгия
      • Brasschaat, Бельгия, 2930
        • Novartis Investigative Site
      • Brugge, Бельгия, 8000
        • Novartis Investigative Site
      • Leuven, Бельгия, 3000
        • Novartis Investigative Site
      • Lodelinsart, Бельгия, 6042
        • Novartis Investigative Site
      • Turnhout, Бельгия, 2300
        • Novartis Investigative Site
  • Бразилия
      • Rio de Janeiro, Бразилия, 20211-030
        • Novartis Investigative Site
      • Sao Paulo - SP, Бразилия, 01323-900
        • Novartis Investigative Site
    • Minas Gerais
      • Belo Horizonte, Minas Gerais, Бразилия, 30130-100
        • Novartis Investigative Site
    • Paraná
      • Curitiba, Paraná, Бразилия, 81520-060
        • Novartis Investigative Site
    • Rio Grande Do Sul
      • Porto Alegre, Rio Grande Do Sul, Бразилия, 90035-903
        • Novartis Investigative Site
    • Santa Catarina
      • Florianopolis, Santa Catarina, Бразилия, 88034-000
        • Novartis Investigative Site
    • São Paulo
      • Sao Paulo, São Paulo, Бразилия, 01236030
        • Novartis Investigative Site
      • Sao Paulo, São Paulo, Бразилия, 08270-070
        • Novartis Investigative Site
  • Венгрия
      • Debrecen, Венгрия, 4012
        • Novartis Investigative Site
      • Szeged, Венгрия, 6725
        • Novartis Investigative Site
  • Германия
    • Baden-Wuerttemberg
      • Stuttgart, Baden-Wuerttemberg, Германия, 70199
        • Novartis Investigative Site
    • Bayern
      • Muenchen, Bayern, Германия, 81675
        • Novartis Investigative Site
    • Niedersachsen
      • Goettingen, Niedersachsen, Германия, 37075
        • Novartis Investigative Site
    • Nordrhein-Westfalen
      • Duesseldorf, Nordrhein-Westfalen, Германия, 40225
        • Novartis Investigative Site
      • Duesseldorf, Nordrhein-Westfalen, Германия, 40479
        • Novartis Investigative Site
      • Duisburg, Nordrhein-Westfalen, Германия, 47166
        • Novartis Investigative Site
    • Sachsen
      • Dresden, Sachsen, Германия, 01307
        • Novartis Investigative Site
  • Гонконг
      • Chai Wan, Гонконг
        • Novartis Investigative Site
      • Hong Kong, Гонконг
        • Novartis Investigative Site
      • Shatin, New Territories, Гонконг
        • Novartis Investigative Site
      • Tuen Mun, Гонконг
        • Novartis Investigative Site
  • Греция
      • Athens,, Греция, 11 527
        • Novartis Investigative Site
      • Larisa, Греция, 41 110
        • Novartis Investigative Site
      • Patra, Греция, 26500
        • Novartis Investigative Site
      • Thessaloniki, Греция, 54642
        • Novartis Investigative Site
      • Thessaloniki, Греция, 54636
        • Novartis Investigative Site
  • Дания
      • Aarhus, Дания, 8000 C
        • Novartis Investigative Site
      • Koebenhavn Oe, Дания, 2100
        • Novartis Investigative Site
  • Израиль
      • Haifa, Израиль, 31096
        • Novartis Investigative Site
      • Holon, Израиль, 58100
        • Novartis Investigative Site
      • Jerusalem, Израиль, 91120
        • Novartis Investigative Site
      • Jerusalem, Израиль, 91031
        • Novartis Investigative Site
      • Kfar Saba, Израиль, 44281
        • Novartis Investigative Site
      • Petach-Tikva, Израиль, 49100
        • Novartis Investigative Site
      • Tel Aviv, Израиль, 64239
        • Novartis Investigative Site
  • Ирландия
      • Dublin, Ирландия, 7
        • Novartis Investigative Site
      • Galway, Ирландия
        • Novartis Investigative Site
      • James Street, Ирландия, 8
        • Novartis Investigative Site
      • Limerick, Ирландия
        • Novartis Investigative Site
      • Tallaght, Dublin, Ирландия, 24
        • Novartis Investigative Site
  • Испания
      • Barcelona, Испания, 08035
        • Novartis Investigative Site
      • Barcelona, Испания, 08036
        • Novartis Investigative Site
      • Gerona, Испания, 17007
        • Novartis Investigative Site
      • La Laguna (Santa Cruz De Tenerife), Испания, 38320
        • Novartis Investigative Site
      • Leon, Испания, 24071
        • Novartis Investigative Site
      • León, Испания, 24071
        • Novartis Investigative Site
      • Madrid, Испания, 28034
        • Novartis Investigative Site
      • Madrid, Испания, 28046
        • Novartis Investigative Site
      • Madrid, Испания, 28007
        • Novartis Investigative Site
      • Majadahonda (Madrid), Испания, 28222
        • Novartis Investigative Site
      • Malaga, Испания, 29010
        • Novartis Investigative Site
      • Málaga, Испания, 29010
        • Novartis Investigative Site
      • Oviedo, Испания, 33006
        • Novartis Investigative Site
      • Palma de Mallorca, Испания, 07198
        • Novartis Investigative Site
      • Palma de Mallorca, Испания, 07014
        • Novartis Investigative Site
      • Pozuelo De Alarcon/Madrid, Испания, 28223
        • Novartis Investigative Site
      • Pozuelo De Alarcón/Madrid, Испания, 28223
        • Novartis Investigative Site
      • Salamanca, Испания, 37007
        • Novartis Investigative Site
      • Valencia, Испания, 46026
        • Novartis Investigative Site
      • Valencia, Испания, 46010
        • Novartis Investigative Site
    • Asturias
      • Oviedo, Asturias, Испания, 33011
        • Novartis Investigative Site
  • Италия
    • Calabria
      • Reggio Calabria, Calabria, Италия, 89100
        • Novartis Investigative Site
    • Emilia-Romagna
      • Modena, Emilia-Romagna, Италия, 41124
        • Novartis Investigative Site
    • Liguria
      • Genova, Liguria, Италия, 10126
        • Novartis Investigative Site
    • Piemonte
      • Novara, Piemonte, Италия, 28100
        • Novartis Investigative Site
    • Toscana
      • Firenze, Toscana, Италия, 50134
        • Novartis Investigative Site
  • Канада
      • Quebec, Канада, G1J 1Z4
        • Novartis Investigative Site
      • Québec, Канада, G1J 1Z4
        • Novartis Investigative Site
    • Ontario
      • Toronto, Ontario, Канада, M5G 2M9
        • Novartis Investigative Site
    • Quebec
      • Montreal, Quebec, Канада, H2L 4M1
        • Novartis Investigative Site
      • Sherbrooke, Quebec, Канада, J1H 5N4
        • Novartis Investigative Site
  • Корея, Республика
      • Seoul, Корея, Республика, 06351
        • Novartis Investigative Site
      • Seoul, Корея, Республика, 138-736
        • Novartis Investigative Site
      • Seoul, Корея, Республика, 135-710
        • Novartis Investigative Site
      • Seoul, Корея, Республика, 137-701
        • Novartis Investigative Site
      • Seoul, Корея, Республика, 06591
        • Novartis Investigative Site
      • Seoul, Корея, Республика, 05505
        • Novartis Investigative Site
  • Мексика
      • Oaxaca, Мексика, 68000
        • Novartis Investigative Site
    • Nuevo León
      • Monterrey, Nuevo León, Мексика, 64460
        • Novartis Investigative Site
  • Норвегия
      • Bergen, Норвегия, N-5021
        • Novartis Investigative Site
      • Oslo, Норвегия, 0027
        • Novartis Investigative Site
  • Перу
      • Lima, Перу, Lima 11
        • Novartis Investigative Site
      • Lima, Перу, Lima 31
        • Novartis Investigative Site
  • Польша
      • Krakow, Польша, 31-501
        • Novartis Investigative Site
      • Legnica, Польша, 59-200
        • Novartis Investigative Site
      • Lublin, Польша, 20-081
        • Novartis Investigative Site
      • Opole, Польша, 45-061
        • Novartis Investigative Site
      • Slupsk, Польша, 76-200
        • Novartis Investigative Site
      • Torun, Польша, 87-100
        • Novartis Investigative Site
  • Пуэрто-Рико
      • San Juan, Пуэрто-Рико, 00927
        • Novartis Investigative Site
  • Российская Федерация
      • Kaluga, Российская Федерация, 248007
        • Novartis Investigative Site
      • Moscow, Российская Федерация, 115478
        • Novartis Investigative Site
      • Moscow, Российская Федерация, 125167
        • Novartis Investigative Site
      • Moscow, Российская Федерация, 129301
        • Novartis Investigative Site
      • Penza, Российская Федерация, 440071
        • Novartis Investigative Site
      • St Petersburg, Российская Федерация, 193024
        • Novartis Investigative Site
      • St'Petersburg, Российская Федерация, 197341
        • Novartis Investigative Site
  • Соединенные Штаты
    • Connecticut
      • Hartford, Connecticut, Соединенные Штаты, 06105
        • Novartis Investigative Site
    • Georgia
      • Atlanta, Georgia, Соединенные Штаты, 30322
        • Novartis Investigative Site
    • Illinois
      • Chicago, Illinois, Соединенные Штаты, 60612
        • Novartis Investigative Site
    • Indiana
      • Anderson, Indiana, Соединенные Штаты, 46016
        • Novartis Investigative Site
    • Missouri
      • Kansas City, Missouri, Соединенные Штаты, 64128
        • Novartis Investigative Site
      • San Luis, Missouri, Соединенные Штаты, 63110
        • Novartis Investigative Site
    • New York
      • Bronx, New York, Соединенные Штаты, 10461
        • Novartis Investigative Site
    • North Carolina
      • Winston-Salem, North Carolina, Соединенные Штаты, 27157
        • Novartis Investigative Site
    • Washington
      • Seattle, Washington, Соединенные Штаты, 98108
        • Novartis Investigative Site
    • Wisconsin
      • Milwaukee, Wisconsin, Соединенные Штаты, 53226
        • Novartis Investigative Site
  • Таиланд
      • Bangkok, Таиланд, 10700
        • Novartis Investigative Site
      • Bangkok, Таиланд, 10400
        • Novartis Investigative Site
      • ChiangMai, Таиланд, 50000
        • Novartis Investigative Site
  • Тайвань
      • Changhua, Тайвань, 500
        • Novartis Investigative Site
      • Kaohsiung, Тайвань, 807
        • Novartis Investigative Site
      • Kaohsiung, Тайвань, 833
        • Novartis Investigative Site
      • Taipei, Тайвань, 112
        • Novartis Investigative Site
  • Турция
      • Ankara, Турция, 06590
        • Novartis Investigative Site
      • Izmir, Турция, 35340
        • Novartis Investigative Site
      • Izmir, Турция, 35100
        • Novartis Investigative Site
      • Samsun, Турция, 55139
        • Novartis Investigative Site
  • Франция
      • Angers Cedex 9, Франция, 49933
        • Novartis Investigative Site
      • Caen Cedex 9, Франция, 14033
        • Novartis Investigative Site
      • Le Mans, Франция, 72000
        • Novartis Investigative Site
      • Paris, Франция, 75010
        • Novartis Investigative Site
      • Paris Cedex 12, Франция, 75571
        • Novartis Investigative Site
      • Pringy Cedex, Франция, 74374
        • Novartis Investigative Site
  • Чехия
      • Brno, Чехия, 625 00
        • Novartis Investigative Site
      • Ostrava, Чехия, 708 52
        • Novartis Investigative Site
      • Praha, Чехия, 128 20
        • Novartis Investigative Site
      • Praha 10, Чехия, 100 34
        • Novartis Investigative Site
      • Praha 2, Чехия, 128 08
        • Novartis Investigative Site
  • Швейцария
      • Aarau, Швейцария, 5001
        • Novartis Investigative Site
      • Bellinzona, Швейцария, 6500
        • Novartis Investigative Site
      • Bern, Швейцария, 3010
        • Novartis Investigative Site
      • Zuerich, Швейцария, 8091
        • Novartis Investigative Site
  • Швеция
      • Goteborg, Швеция, SE-413 45
        • Novartis Investigative Site
      • Göteborg, Швеция, SE-413 45
        • Novartis Investigative Site
      • Stockholm, Швеция, SE-141 86
        • Novartis Investigative Site
      • Uppsala, Швеция, SE-751 85
        • Novartis Investigative Site

Критерии участия

Исследователи ищут людей, которые соответствуют определенному описанию, называемому критериям приемлемости. Некоторыми примерами этих критериев являются общее состояние здоровья человека или предшествующее лечение.

Критерии приемлемости

Возраст, подходящий для обучения

18 лет и старше (Взрослый, Пожилой взрослый)

Принимает здоровых добровольцев

Нет

Полы, имеющие право на обучение

Все

Описание

Inclusion Criteria:

  • Age >=18 years (For subjects in Taiwan, Age >= 20 years)
  • MDS by World Health Organization (WHO) or French-American-British (FAB) classification
  • Intermediate 1, intermediate 2 or high risk MDS by IPSS
  • At least one platelet count < 75 Gi/L
  • Eastern Cooperative Oncology Group (ECOG) Status 0-2
  • Adequate baseline organ function defined by the criteria below: total bilirubin =< 1.5x the upper limit of normal (ULN) except for Gilbert's syndrome or cases clearly not indicative of inadequate liver function (i.e. elevation of indirect [haemolytic] bilirubin in the absence of alanine aminotransferase [ALT] abnormality); ALT =< 2.5xULN; creatinine =< 2.5xULN
  • Subjects with a corrected QT interval (QTc) <450 milliseconds (msec) or <480msec for subjects with bundle branch block. The QTc is the QT interval corrected for heart rate according to Fridericia's formula (QTcF), machine or manual overread. For subject eligibility and withdrawal, QTcF will be used. For purposes of data analysis, QTcF will be used. The QTc should be based on single or averaged QTc values of triplicate electrocardiograms (ECGs) obtained over a brief recording period
  • Subject is able to understand and comply with protocol requirements and instructions
  • Subject has signed and dated informed consent
  • Women must be either of non-child bearing potential, or women with child-bearing potential and men with reproductive potential must be willing to practice acceptable methods of birth control during the study
  • Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days of first dose of study treatment and agree to use effective contraception during the study and for 3 months following the last dose of study treatment
  • Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception from time of randomization until 16 weeks after the last dose of study treatment
  • French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category

Exclusion Criteria:

  • Previous treatment with hypomethylating agent or induction chemotherapy for MDS
  • Proliferative type chronic myelomonocytic leukemia with white blood cell count >12 Gi/L at any time during the 28 days before Day 1
  • History of treatment with eltrombopag, romiplostim or other thrombopoietin receptor (TPO-R) agonists
  • Previous allogeneic stem-cell transplantation
  • Known thrombophilic risk factors. Exception: Subjects for whom the potential benefits of participating in the study outweigh the potential risks of thromboembolic events, as determined by the investigator
  • Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of investigational product (eltrombopag/placebo)
  • Active and uncontrolled infections, including hepatitis B or C
  • Human Immunodeficiency Virus (HIV) infection
  • Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to eltrombopag or its excipient, or azacitidine, that contraindicates the subjects' participation
  • Pregnant or lactating female
  • Any serious and/or unstable pre-existing medical condition (including any advanced malignancy other than the disease under study), psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance with the study procedures
  • French subjects: the French subject has participated in any study using an investigational drug during the previous 30 days

Учебный план

В этом разделе представлена ​​подробная информация о плане исследования, в том числе о том, как планируется исследование и что оно измеряет.

Как устроено исследование?

Детали дизайна

  • Основная цель: Уход
  • Распределение: Рандомизированный
  • Интервенционная модель: Параллельное назначение
  • Маскировка: Двойной

Оружие и интервенции

Группа участников / Армия
Вмешательство/лечение
Экспериментальный: Eltrombopag
Eligible subject will receive a starting dose of eltrombopag of 200 milligrams (mg) (100 mg for subjects of East Asian heritage). Dose modifications of eltrombopag will be permitted by 100 mg increments (50 mg increments for East Asians) to a lowest dose of 100 mg (50 mg for East Asian heritage) or a maximum dose of 300 mg (150 mg for East Asian heritage) in order to maintain platelet counts at a safe and effective level (i.e. a level sufficient to avoid platelet transfusions and bleeding events). Subjects will receive azacitidine 75 mg/meter^2 subcutaneously once daily for 7 days (+/- 3 day treatment window permitted) every 28 days, for at least 6 cycles if tolerated and until they are no longer receiving benefit (defined as at least stable disease per the investigator's assessment) or until disease progression, death, or unacceptable toxicity/adverse event. The subject may receive eltrombopag daily for the full 28 days each cycle for as long as the subject is receiving azacitidine
Лекарство: Eltrombopag
Eltrombopag will be round film-coated tablets containing eltrombopag equivalent to 50 mg (white to off-white), 200 mg and 300 mg (green) of eltrombopag free acid
Лекарство: Azacitidine
Subcutaneous Injection (IV if local standard)
Плацебо Компаратор: Placebo
Eligible subject will receive eltrombopag matching placebo. Subjects will receive azacitidine 75 mg/meter^2 subcutaneously once daily for 7 days (+/- 3 day treatment window permitted) every 28 days, for at least 6 cycles if tolerated and until they are no longer receiving benefit (defined as at least stable disease per the investigator's assessment) or until disease progression, death, or unacceptable toxicity/adverse event. The subject may receive eltrombopag daily for the full 28 days each cycle for as long as the subject is receiving azacitidine
Лекарство: Azacitidine
Subcutaneous Injection (IV if local standard)
Лекарство: Placebo
Eltrombopag matching placebo tablets
Лекарство: Placebo
Eltrombopag matching placebo tablets will be supplied

Что измеряет исследование?

Первичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Number of Participants Who Were Platelet Transfusion Independent During Cycles 1-4 of Azacitidine Therapy
Временное ограничение: 4 cycles (Cycle = 28 days)
A subject is defined as being platelet transfusion independent if they received no platelet transfusions within the first 4 cycles of treatment with azacitidine. Subjects who died or withdrew from investigational product within the first four cycles were treated as failures (i.e. not transfusion independent) in the analysis
4 cycles (Cycle = 28 days)

Вторичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Overall Survival (OS)
Временное ограничение: Randomization until death or end of study, approximately 2 years
Overall survival is defined as the time from randomization until death due to any cause and deaths have been presented. Subjects still alive at the time of the analysis and subjects who have withdrawn from the study will be censored at the time of last contact
Randomization until death or end of study, approximately 2 years
Summary of Progression Free Survival From Investigator Assessment (ITT)
Временное ограничение: First day of each cycle (Cycles 3+), at the end of therapy visit and every 3 months in follow-up for approximately 2 years
Progression-free survival, defined as the time from randomization until either disease progression or death. The modified 2006 IWG criteria for MDS used for progression assessment For patients with: Less than 5% BM blasts: ≥ 50% increase in blasts to > 5% blasts; 5% - <10% BM blasts: ≥ 50% increase to > 10% blasts; 10% - <20% BM blasts: ≥ 50% increase to > 20% blasts; 20% - 30% BM blasts: ≥ 50% increase to > 30% blasts
First day of each cycle (Cycles 3+), at the end of therapy visit and every 3 months in follow-up for approximately 2 years
Summary of Progression Free Survival From Central Review (ITT)
Временное ограничение: First day of each cycle (Cycles 3+), at the end of therapy visit and every 3 months in follow-up for approximately 2 years

Progression-free survival, defined as the time from randomization until either disease progression or death. The modified 2006 IWG criteria for MDS used for progression assessment For patients with:

Less than 5% BM blasts: ≥ 50% increase in blasts to > 5% blasts; 5% - <10% BM blasts: ≥ 50% increase to > 10% blasts; 10% - <20% BM blasts: ≥ 50% increase to > 20% blasts; 20% - 30% BM blasts: ≥ 50% increase to > 30% blasts
First day of each cycle (Cycles 3+), at the end of therapy visit and every 3 months in follow-up for approximately 2 years
Summary of AML Progression From Investigator Assessment and Central Review (ITT)
Временное ограничение: First day of each cycle (Cycles 3+), at the end of therapy visit and every 3 months in follow-up for approximately 2 years

Progression to AML in MDS patients with baseline bone marrow blast < 20% was defined as meeting definition of disease progression according to the modified 2006 IWG response criteria for MDS with the additional requirement that bone marrow blast or peripheral blast increases from < 20% at baseline to ≥ 20% postbaseline. Progression assessment For patients with:

Less than 5% BM blasts: ≥ 50% increase in blasts to > 5% blasts; 5% - <10% BM blasts: ≥ 50% increase to > 10% blasts; 10% - <20% BM blasts: ≥ 50% increase to > 20% blasts; 20% - 30% BM blasts: ≥ 50% increase to > 30% blasts
First day of each cycle (Cycles 3+), at the end of therapy visit and every 3 months in follow-up for approximately 2 years
Best Disease Response From Investigator Assessment (ITT)
Временное ограничение: At end of Cycle 6 (cycle=28 days) or end of therapy, whichever came first
Best disease response is categorized as complete remission (CR), partial remission (PR), or marrow CR, stable disease, disease progression, or as non-evaluable; according to modified 2006 International Working Group (IWG) criteria for MDS
At end of Cycle 6 (cycle=28 days) or end of therapy, whichever came first
Best Disease Response From Central Review (ITT)
Временное ограничение: At end of Cycle 6 (cycle=28 days) or end of therapy, whichever came first
Best disease response is categorized as complete remission (CR), partial remission (PR), or marrow CR, stable disease, disease progression, or as non-evaluable; according to modified 2006 International Working Group (IWG) criteria for MDS
At end of Cycle 6 (cycle=28 days) or end of therapy, whichever came first
Hematologic Improvement (HI) in Platelets, Neutrophils, and Hemoglobin Based on the Modified IWG Criteria for MDS (ITT)
Временное ограничение: From Day 1 to 4-week follow-up (samples collected weekly in Cycle 1, Days 1 and 15 in Cycles 2-6 and Day 1 of Cycles >=7)
HI based on the modified IWG criteria for MDS. HI - Platelets (BL <100Gi/L), response criteria= BL <20: increase to>20 and 100% at least for 56 days or BL >=20: absolute increase of >=30. HI - Neutrophils (BL <1.0 Gi/L), response criteria=100% increase and an absolute increase >0.5 Gi/L over BL for at least 56 days. HI-Hemoglobin (BL <g/dL), response criteria=Hgb increase by >=1.5 g/dL over BL, RBC transfusions(given for Hgb<=9.0) reduced by >=4 per 8w from BL
From Day 1 to 4-week follow-up (samples collected weekly in Cycle 1, Days 1 and 15 in Cycles 2-6 and Day 1 of Cycles >=7)
Number of Participants Who Were Platelet Transfusion Independent (ITT Set)
Временное ограничение: From Day 1 to end of study treatment up to approximately 2 years
Platelet transfusion independence is defined for each cycle as the number of participants who continue to the end of a cycle without requiring a platelet transfusion
From Day 1 to end of study treatment up to approximately 2 years
Bleeding Adverse Events (AEs) >= Grade 3
Временное ограничение: From Day 1 to 4-week follow-up up to approximately 2 years
Bleeding will be assessed by recording AEs or serious adverse events (SAEs) as graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0
From Day 1 to 4-week follow-up up to approximately 2 years
Number of of Subjects With Azacitidine Dose Delays, Dose Reductions, Interruptions
Временное ограничение: From Day 1 to 4-week follow-up up to approximately 2 years
The proportion of subjects with any delay, reduction or interruption in dosage of Azacitidine excluding those for non-medical reasons will be analyzed
From Day 1 to 4-week follow-up up to approximately 2 years
Response Levels in All Domains of Euroquol-5 Dimensions of Health, 3 Response Levels (EQ-5D-3L™)
Временное ограничение: From Day 1 to 4-week follow-up up to approximately 2 years
The EQ-5D is a general health status and health utility measure which captures 5 dimensions of health state: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. (EQ-5D is a trademark of the Stichting EuroQol Group) . C=cycle, D=Day
From Day 1 to 4-week follow-up up to approximately 2 years
Functional Assessment of Chronic Disease Therapy-fatigue Subscale (FACIT-Fatigue) (ITT)
Временное ограничение: From Day 1 to 4-week follow-up (Approximate median 9 Cycles+4 weeks follow-up) up to approximately 2 years
The FACIT-Fatigue subscale measures severity and impact of fatigue on functioning and Health Related QoL experienced in the past 7 days. Scale is a 13 item measure of fatigure. Items are scored on a 0-4 response scale ranging from "not at all" to "very much so". All items are summed to create a single fatigure score with a range from 0 to 52. Items are reverse scored when appropriate to provide a scale in which higher scores represent better functioning or less fatiigue (The FACIT Fatigue Scale is owned by David Cella, Ph.D.)
From Day 1 to 4-week follow-up (Approximate median 9 Cycles+4 weeks follow-up) up to approximately 2 years
Medical Resource Utilization (MRU): Event -Hospitalizations Inpatient and Outpatient
Временное ограничение: From Day 1 to 4-week follow-up (Approximate median 9 Cycles+4 weeks follow-up) up to approximately 2 years
MRU data will be collected for each subject. Events corresponding to unscheduled (not scheduled per protocol) hospitalizations
From Day 1 to 4-week follow-up (Approximate median 9 Cycles+4 weeks follow-up) up to approximately 2 years
Medical Resource Utilization (MRU): Event and Use of Site Specific Medical Resources - Non-study Laboratory Tests
Временное ограничение: From Day 1 to 4-week follow-up (Approximate median 9 Cycles+4 weeks follow-up) up to approximately 2 years
MRU data will be collected for each subject. Events corresponding to unscheduled (not scheduled per protocol) hospitalizations, office visits including consultations, laboratory and diagnostic tests (lab results, imaging etc.), and procedures prior to therapy initiation and during therapy will be collected
From Day 1 to 4-week follow-up (Approximate median 9 Cycles+4 weeks follow-up) up to approximately 2 years
Medical Resource Utilization (MRU): Use of Site Specific Medical Resources
Временное ограничение: From Day 1 to 4-week follow-up (Approximate median 9 Cycles+4 weeks follow-up) up to approximately 2 years
MRU data will be collected for each subject. Events corresponding to unscheduled (not scheduled per protocol) hospitalizations, office visits including consultations, laboratory and diagnostic tests (lab results, imaging etc.), and procedures prior to therapy initiation and during therapy will be collected
From Day 1 to 4-week follow-up (Approximate median 9 Cycles+4 weeks follow-up) up to approximately 2 years
Summary of Post-Hoc Estimates of Steady-state Eltrombopag Cmax and Cmin Pharmacokinetic Parameters for a 50 mg Dose
Временное ограничение: Cycle 1, Week 2: Pre-dose, 1.5 and 3 hour post dose; Cycle 1, Week 3: 4, 5.5, and 7 hours post dose
Eltrombopag concentrations were analyzed using a population PK model along with data from other studies in healthy volunteers and in patients with MDS and/or AML. Post-hoc PK parameters were derived. Only patients from this study were included (163)
Cycle 1, Week 2: Pre-dose, 1.5 and 3 hour post dose; Cycle 1, Week 3: 4, 5.5, and 7 hours post dose
Summary of Post-Hoc Estimates of Steady-state Eltrombopag AUC0 Infinity Pharmacokinetic Parameters for a 50 mg Dose
Временное ограничение: Cycle 1, Week 2: Pre-dose, 1.5 and 3 hour post dose; Cycle 1, Week 3: 4, 5.5, and 7 hours post dose
Eltrombopag concentrations were analyzed using a population PK model along with data from other studies in healthy volunteers and in patients with MDS and/or AML. Post-hoc PK parameters were derived. Only patients from this study were included (163)
Cycle 1, Week 2: Pre-dose, 1.5 and 3 hour post dose; Cycle 1, Week 3: 4, 5.5, and 7 hours post dose
AUC0-infinity -Pharmacokinetic(s) Parameter of Azacitidine
Временное ограничение: Cycle 2 Day 1: Pre-dose, 15 min, 0.5, 1, 2 and 4 hr post dose
An analysis of variance (ANOVA) on AUC0-infinity. The PK parameters were log transformed prior to analysis. The model included treatment as a fixed effect. Point estimates and their associated 90% CI were constructed for the differences in PK parameter values. The point estimates and their associated 90% CI were then back transformed to provide point estimates and 90% CI for the azacitidine + eltrombopag:azacitidine + placebo PK parameter ratios.
Cycle 2 Day 1: Pre-dose, 15 min, 0.5, 1, 2 and 4 hr post dose
Cmax -Pharmacokinetic Parameter of Azacitidine
Временное ограничение: Cycle 2 Day 1: Pre-dose, 15 min, 0.5, 1, 2 and 4 hr post dose
An analysis of variance (ANOVA) on Cmax . The PK parameters were log transformed prior to analysis. The model included treatment as a fixed effect. Point estimates and their associated 90% CI were constructed for the differences in PK parameter values. The point estimates and their associated 90% CI were then back transformed to provide point estimates and 90% CI for the azacitidine + ltrombopag:azacitidine + placebo PK parameter ratios.
Cycle 2 Day 1: Pre-dose, 15 min, 0.5, 1, 2 and 4 hr post dose

Соавторы и исследователи

Здесь вы найдете людей и организации, участвующие в этом исследовании.

Спонсор

Novartis Pharmaceuticals

Публикации и полезные ссылки

Лицо, ответственное за внесение сведений об исследовании, добровольно предоставляет эти публикации. Это может быть что угодно, связанное с исследованием.

Общие публикации

Даты записи исследования

Эти даты отслеживают ход отправки отчетов об исследованиях и сводных результатов на сайт ClinicalTrials.gov. Записи исследований и сообщаемые результаты проверяются Национальной медицинской библиотекой (NLM), чтобы убедиться, что они соответствуют определенным стандартам контроля качества, прежде чем публиковать их на общедоступном веб-сайте.

Изучение основных дат

Начало исследования (Действительный)

10 июня 2014 г.

Первичное завершение (Действительный)

30 апреля 2016 г.

Завершение исследования (Действительный)

30 апреля 2016 г.

Даты регистрации исследования

Первый отправленный

5 июня 2014 г.

Впервые представлено, что соответствует критериям контроля качества

5 июня 2014 г.

Первый опубликованный (Оценивать)

9 июня 2014 г.

Обновления учебных записей

Последнее опубликованное обновление (Действительный)

12 декабря 2017 г.

Последнее отправленное обновление, отвечающее критериям контроля качества

12 ноября 2017 г.

Последняя проверка

1 сентября 2017 г.

Дополнительная информация

Термины, связанные с этим исследованием

Ключевые слова

Дополнительные соответствующие термины MeSH

Другие идентификационные номера исследования

  • 112121

Информация о лекарствах и устройствах, исследовательские документы

Изучает лекарственный продукт, регулируемый FDA США.

Да

Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.

Нет

Эта информация была получена непосредственно с веб-сайта clinicaltrials.gov без каких-либо изменений. Если у вас есть запросы на изменение, удаление или обновление сведений об исследовании, обращайтесь по адресу register@clinicaltrials.gov. Как только изменение будет реализовано на clinicaltrials.gov, оно будет автоматически обновлено и на нашем веб-сайте. .

Подписаться