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)

NCT ID: NCT02158936

Last Updated: 2017-12-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 356 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-06-10
• Study Completion Date: 2016-04-30

Brief Summary

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.

Conditions

Thrombocytopaenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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

Group Type: EXPERIMENTAL

Eltrombopag

Intervention Type: DRUG

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

Azacitidine

Intervention Type: DRUG

Subcutaneous Injection (IV if local standard)

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

Group Type: PLACEBO_COMPARATOR

Azacitidine

Intervention Type: DRUG

Subcutaneous Injection (IV if local standard)

Placebo

Intervention Type: DRUG

Eltrombopag matching placebo tablets

Placebo

Intervention Type: DRUG

Eltrombopag matching placebo tablets will be supplied

Interventions

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

Intervention Type: DRUG

Azacitidine

Subcutaneous Injection (IV if local standard)

Intervention Type: DRUG

Placebo

Eltrombopag matching placebo tablets

Intervention Type: DRUG

Placebo

Eltrombopag matching placebo tablets will be supplied

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Hartford, Connecticut, United States

Novartis Investigative Site

Atlanta, Georgia, United States

Novartis Investigative Site

Chicago, Illinois, United States

Novartis Investigative Site

Anderson, Indiana, United States

Novartis Investigative Site

Kansas City, Missouri, United States

Novartis Investigative Site

St Louis, Missouri, United States

Novartis Investigative Site

The Bronx, New York, United States

Novartis Investigative Site

Winston-Salem, North Carolina, United States

Novartis Investigative Site

Seattle, Washington, United States

Novartis Investigative Site

Milwaukee, Wisconsin, United States

Novartis Investigative Site

Buenos Aires, , Argentina

Novartis Investigative Site

Buenos Aires, , Argentina

Novartis Investigative Site

Buenos Aires, , Argentina

Novartis Investigative Site

Santa Fe, , Argentina

Novartis Investigative Site

Kogarah, New South Wales, Australia

Novartis Investigative Site

Adelaide, South Australia, Australia

Novartis Investigative Site

Clayton, Victoria, Australia

Novartis Investigative Site

East Melbourne, Victoria, Australia

Novartis Investigative Site

Melbourne, Victoria, Australia

Novartis Investigative Site

Graz, , Austria

Novartis Investigative Site

Innsbruck, , Austria

Novartis Investigative Site

Linz, , Austria

Novartis Investigative Site

Rankweil, , Austria

Novartis Investigative Site

Salzburg, , Austria

Novartis Investigative Site

Steyr, , Austria

Novartis Investigative Site

Vienna, , Austria

Novartis Investigative Site

Brasschaat, , Belgium

Novartis Investigative Site

Bruges, , Belgium

Novartis Investigative Site

Leuven, , Belgium

Novartis Investigative Site

Lodelinsart, , Belgium

Novartis Investigative Site

Turnhout, , Belgium

Novartis Investigative Site

Belo Horizonte, Minas Gerais, Brazil

Novartis Investigative Site

Curitiba, Paraná, Brazil

Novartis Investigative Site

Porto Alegre, Rio Grande do Sul, Brazil

Novartis Investigative Site

Florianópolis, Santa Catarina, Brazil

Novartis Investigative Site

São Paulo, São Paulo, Brazil

Novartis Investigative Site

São Paulo, São Paulo, Brazil

Novartis Investigative Site

Rio de Janeiro, , Brazil

Novartis Investigative Site

Sao Paulo - SP, , Brazil

Novartis Investigative Site

Toronto, Ontario, Canada

Novartis Investigative Site

Montreal, Quebec, Canada

Novartis Investigative Site

Québec, Quebec, Canada

Novartis Investigative Site

Sherbrooke, Quebec, Canada

Novartis Investigative Site

Québec, , Canada

Novartis Investigative Site

Brno, , Czechia

Novartis Investigative Site

Ostrava, , Czechia

Novartis Investigative Site

Prague, , Czechia

Novartis Investigative Site

Prague, , Czechia

Novartis Investigative Site

Prague, , Czechia

Novartis Investigative Site

Aarhus, , Denmark

Novartis Investigative Site

Koebenhavn Oe, , Denmark

Novartis Investigative Site

Angers, , France

Novartis Investigative Site

Caen, , France

Novartis Investigative Site

Le Mans, , France

Novartis Investigative Site

Paris, , France

Novartis Investigative Site

Paris, , France

Novartis Investigative Site

Pringy, , France

Novartis Investigative Site

Stuttgart, Baden-Wurttemberg, Germany

Novartis Investigative Site

Munich, Bavaria, Germany

Novartis Investigative Site

Göttingen, Lower Saxony, Germany

Novartis Investigative Site

Duisburg, North Rhine-Westphalia, Germany

Novartis Investigative Site

Düsseldorf, North Rhine-Westphalia, Germany

Novartis Investigative Site

Düsseldorf, North Rhine-Westphalia, Germany

Novartis Investigative Site

Dresden, Saxony, Germany

Novartis Investigative Site

Athens, , Greece

Novartis Investigative Site

Larissa, , Greece

Novartis Investigative Site

Pátrai, , Greece

Novartis Investigative Site

Thessaloniki, , Greece

Novartis Investigative Site

Thessaloniki, , Greece

Novartis Investigative Site

Chai Wan, , Hong Kong

Novartis Investigative Site

Hong Kong, , Hong Kong

Novartis Investigative Site

Shatin, New Territories, , Hong Kong

Novartis Investigative Site

Tuenmen, , Hong Kong

Novartis Investigative Site

Debrecen, , Hungary

Novartis Investigative Site

Szeged, , Hungary

Novartis Investigative Site

Dublin, , Ireland

Novartis Investigative Site

Galway, , Ireland

Novartis Investigative Site

James Street, , Ireland

Novartis Investigative Site

Limerick, , Ireland

Novartis Investigative Site

Tallaght, Dublin, , Ireland

Novartis Investigative Site

Haifa, , Israel

Novartis Investigative Site

Holon, , Israel

Novartis Investigative Site

Jerusalem, , Israel

Novartis Investigative Site

Jerusalem, , Israel

Novartis Investigative Site

Kfar Saba, , Israel

Novartis Investigative Site

Petah Tikva, , Israel

Novartis Investigative Site

Tel Aviv, , Israel

Novartis Investigative Site

Reggio Calabria, Calabria, Italy

Novartis Investigative Site

Modena, Emilia-Romagna, Italy

Novartis Investigative Site

Genoa, Liguria, Italy

Novartis Investigative Site

Novara, Piedmont, Italy

Novartis Investigative Site

Florence, Tuscany, Italy

Novartis Investigative Site

Monterrey, Nuevo León, Mexico

Novartis Investigative Site

Oaxaca City, , Mexico

Novartis Investigative Site

Bergen, , Norway

Novartis Investigative Site

Oslo, , Norway

Novartis Investigative Site

Lima, , Peru

Novartis Investigative Site

Lima, , Peru

Novartis Investigative Site

Krakow, , Poland

Novartis Investigative Site

Legnica, , Poland

Novartis Investigative Site

Lublin, , Poland

Novartis Investigative Site

Opole, , Poland

Novartis Investigative Site

Słupsk, , Poland

Novartis Investigative Site

Torun, , Poland

Novartis Investigative Site

San Juan, , Puerto Rico

Novartis Investigative Site

Kaluga, , Russia

Novartis Investigative Site

Moscow, , Russia

Novartis Investigative Site

Moscow, , Russia

Novartis Investigative Site

Moscow, , Russia

Novartis Investigative Site

Penza, , Russia

Novartis Investigative Site

Saint Petersburg, , Russia

Novartis Investigative Site

St'Petersburg, , Russia

Novartis Investigative Site

Seoul, , South Korea

Novartis Investigative Site

Seoul, , South Korea

Novartis Investigative Site

Seoul, , South Korea

Novartis Investigative Site

Seoul, , South Korea

Novartis Investigative Site

Seoul, , South Korea

Novartis Investigative Site

Seoul, , South Korea

Novartis Investigative Site

Oviedo, Principality of Asturias, Spain

Novartis Investigative Site

Barcelona, , Spain

Novartis Investigative Site

Barcelona, , Spain

Novartis Investigative Site

Girona, , Spain

Novartis Investigative Site

La Laguna (Santa Cruz de Tenerife), , Spain

Novartis Investigative Site

León, , Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Majadahonda (Madrid), , Spain

Novartis Investigative Site

Málaga, , Spain

Novartis Investigative Site

Oviedo, , Spain

Novartis Investigative Site

Palma de Mallorca, , Spain

Novartis Investigative Site

Palma de Mallorca, , Spain

Novartis Investigative Site

Pozuelo de Alarcon/Madrid, , Spain

Novartis Investigative Site

Pozuelo de Alarcón/Madrid, , Spain

Novartis Investigative Site

Salamanca, , Spain

Novartis Investigative Site

Valencia, , Spain

Novartis Investigative Site

Valencia, , Spain

Novartis Investigative Site

Gothenburg, , Sweden

Novartis Investigative Site

Stockholm, , Sweden

Novartis Investigative Site

Uppsala, , Sweden

Novartis Investigative Site

Aarau, , Switzerland

Novartis Investigative Site

Bellinzona, , Switzerland

Novartis Investigative Site

Bern, , Switzerland

Novartis Investigative Site

Zurich, , Switzerland

Novartis Investigative Site

Changhua, , Taiwan

Novartis Investigative Site

Kaohsiung City, , Taiwan

Novartis Investigative Site

Kaohsiung City, , Taiwan

Novartis Investigative Site

Taipei, , Taiwan

Novartis Investigative Site

Bangkok, , Thailand

Novartis Investigative Site

Bangkok, , Thailand

Novartis Investigative Site

Chiang Mai, , Thailand

Novartis Investigative Site

Ankara, , Turkey (Türkiye)

Novartis Investigative Site

Izmir, , Turkey (Türkiye)

Novartis Investigative Site

Izmir, , Turkey (Türkiye)

Novartis Investigative Site

Samsun, , Turkey (Türkiye)

Countries

United States; Argentina; Australia; Austria; Belgium; Brazil; Canada; Czechia; Denmark; France; Germany; Greece; Hong Kong; Hungary; Ireland; Israel; Italy; Mexico; Norway; Peru; Poland; Puerto Rico; Russia; South Korea; Spain; Sweden; Switzerland; Taiwan; Thailand; Turkey (Türkiye)

References

Dickinson M, Cherif H, Fenaux P, Mittelman M, Verma A, Portella MSO, Burgess P, Ramos PM, Choi J, Platzbecker U; SUPPORT study investigators. Azacitidine with or without eltrombopag for first-line treatment of intermediate- or high-risk MDS with thrombocytopenia. Blood. 2018 Dec 20;132(25):2629-2638. doi: 10.1182/blood-2018-06-855221. Epub 2018 Oct 10.

Reference Type: DERIVED

PMID: 30305280 (View on PubMed)

Other Identifiers

112121

Identifier Type: -

Identifier Source: org_study_id