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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. listopadu 2017 aktualizováno: 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.

Přehled studie

Postavení

Ukončeno

Podmínky

Intervence / Léčba

Typ studie

Intervenční

Zápis (Aktuální)

356

Fáze

  • Fáze 3

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní místa

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

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

18 let a starší (Dospělý, Starší dospělý)

Přijímá zdravé dobrovolníky

Ne

Pohlaví způsobilá ke studiu

Všechno

Popis

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

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

  • Primární účel: Léčba
  • Přidělení: Randomizované
  • Intervenční model: Paralelní přiřazení
  • Maskování: Dvojnásobek

Zbraně a zásahy

Skupina účastníků / Arm
Intervence / Léčba
Experimentální: 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
Lék: 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
Lék: Azacitidine
Subcutaneous Injection (IV if local standard)
Komparátor placeba: 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
Lék: Azacitidine
Subcutaneous Injection (IV if local standard)
Lék: Placebo
Eltrombopag matching placebo tablets
Lék: Placebo
Eltrombopag matching placebo tablets will be supplied

Co je měření studie?

Primární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Number of Participants Who Were Platelet Transfusion Independent During Cycles 1-4 of Azacitidine Therapy
Časové okno: 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)

Sekundární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Overall Survival (OS)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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
Časové okno: 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
Časové okno: 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™)
Časové okno: 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)
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

Novartis Pharmaceuticals

Publikace a užitečné odkazy

Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.

Obecné publikace

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia (Aktuální)

10. června 2014

Primární dokončení (Aktuální)

30. dubna 2016

Dokončení studie (Aktuální)

30. dubna 2016

Termíny zápisu do studia

První předloženo

5. června 2014

První předloženo, které splnilo kritéria kontroly kvality

5. června 2014

První zveřejněno (Odhad)

9. června 2014

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Aktuální)

12. prosince 2017

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

12. listopadu 2017

Naposledy ověřeno

1. září 2017

Více informací

Termíny související s touto studií

Klíčová slova

Další relevantní podmínky MeSH

Další identifikační čísla studie

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Studuje lékový produkt regulovaný americkým FDA

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Studuje produkt zařízení regulovaný americkým úřadem FDA

Ne

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