A Study to Compare the Efficacy and Safety of Oral Azacitidine Plus Best Supportive Care (BSC) Versus Placebo Plus BSC in Participants With International Prognostic Scoring System Revised (IPSS-R) Low- or Intermediate-risk Myelodysplastic Syndrome (MDS)

Myelodysplastic Syndromes Clinical Trial

Official title:

A Phase 2/3, Multicenter, Randomized, Dose Optimization (Part I), Double-blind (Part II) Study to Compare the Efficacy and Safety of Oral Azacitidine (Oral-Aza, ONUREG®) Plus Best Supportive Care (BSC) Versus Placebo Plus BSC in Participants With IPSS-R Low- or Intermediate-risk Myelodysplastic Syndrome (MDS)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05469737
• Other study ID #: CA055-026
• Secondary ID: U1111-1276-5463
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: December 14, 2022
• Est. completion date: July 29, 2026

Study information

• Verified date: April 2024
• Source: Bristol-Myers Squibb
• Contact: BMS Study Connect Contact Center http://www.bmsstudyconnect.com
• Phone: 855-907-3286
• Email: Clinical.Trials[@]bms.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety and efficacy of oral azacitidine in participants with low to intermediate International Prognostic Scoring System Revised (IPSS-R) myelodysplastic syndrome (MDS).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 230
• Est. completion date: July 29, 2026
• Est. primary completion date: January 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participant has a documented diagnosis of MDS according to WHO 2016 classification that meets International Prognostic Scoring System Revised (IPSS-R) classification of low- or intermediate-risk disease (IPSS-R score between 1.5 and 4.5). MDS diagnosis, WHO classification, and IPSS-R risk classification will be prospectively determined by independent central pathology and cytogenetics review, and applicable central laboratory results.
• Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.

Exclusion Criteria:

• Participants with prior malignancies must have an expected median life expectancy of at least 12 months at the time of inclusion and no active treatment of any sort for at least 24 weeks prior to randomization (including but not limited to immunotherapy or targeted therapy)
• Hypoplastic Myelodysplastic Syndrome (MDS) with a marrow cellularity of = 10%
• Participants diagnosed with MDS with excess blasts-2 (MDS-EB2)
• Prior treatment with azacitidine (any formulation), decitabine, or other hypomethylating agent Other protocol-defined inclusion/exclusion criteria apply

Related Conditions & MeSH terms

• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• Oral Azacitidine
Specified dose on specified days
• Placebo for Oral Azacitidine
Specified dose on specified days

Locations

Country	Name	City	State
Argentina	Local Institution - 0039	ABB	Ciudad Autónoma De Buenos Aires
Argentina	Centro Mdico "Barrio Parque"	Buenos Aires
Argentina	Local Institution - 0021	Buenos Aires	Ciudad Autónoma De Buenos Aires
Argentina	Local Institution - 0022	Buenos Aires
Argentina	Local Institution - 0050	Buenos Aires
Argentina	Local Institution - 0070	Pilar	Buenos Aires
Australia	Local Institution - 0006	Clayton	Victoria
Australia	Local Institution - 0144	Darlinghurst	New South Wales
Australia	Local Institution - 0069	Heidelberg	Victoria
Australia	Local Institution - 0145	Macquarie University	New South Wales
Australia	Local Institution - 0003	Melbourne
Australia	Local Institution - 0004	Melbourne	Victoria
Australia	Local Institution - 0018	Melbourne	Victoria
Australia	Local Institution - 0146	Wollongong	New South Wales
Austria	Local Institution - 0034	Linz	Oberösterreich
Austria	Local Institution - 0074	Salzburg
Austria	Local Institution - 0029	Vienna	Wien
Canada	Local Institution - 0091	Calgary	Alberta
Canada	Local Institution - 0090	Montréal	Quebec
Canada	Local Institution - 0008	Toronto	Ontario
Canada	Local Institution - 0015	Toronto	Ontario
China	Local Institution - 0171	Beijing	Beijing
China	Local Institution - 0179	Changchun	Jilin
China	Local Institution - 0168	Changsha	Hunan
China	Local Institution - 0167	Guangzhou	Guangdong
China	Local Institution - 0141	Hangzhou	Zhejiang
China	Local Institution - 0169	Jinan	Shandong
China	Local Institution - 0162	Nanjing	Jiangsu
China	Local Institution - 0161	Ningbo	Zhejiang
China	Local Institution - 0164	Qingdao	Shandong
China	Local Institution - 0166	Shenyang	Liaoning
China	Local Institution - 0163	Suzhou	Jiangsu
China	Local Institution - 0165	Taiyuan	Shanxi
China	Local Institution - 0156	Wuhan	Hubei
China	Local Institution - 0157	Wuhan	Hubei
China	Local Institution - 0160	Xian	Shaanxi
China	Local Institution - 0170	Zhengzhou
Czechia	Local Institution - 0009	Brno	Brno-mesto
Czechia	Local Institution - 0060	Hradec Kralove
Czechia	Local Institution - 0045	Praha 2
Denmark	Local Institution - 0116	Aalborg	Nordjylland
Denmark	Local Institution - 0115	Aarhus	Midtjylland
Denmark	Local Institution - 0114	Odense	Syddanmark
France	Local Institution - 0094	Angers	Maine-et-Loire
France	Local Institution - 0056	Lille	Nord
France	Local Institution - 0025	Nice	Alpes-Maritimes
France	Local Institution - 0082	Paris
France	Local Institution - 0063	Pessac	Aquitaine
France	Local Institution - 0024	Tours	Indre-et-Loire
France	Local Institution - 0085	Villejuif	Val-de-Marne
Germany	Local Institution - 0037	Dresden
Germany	Local Institution - 0081	Duisburg	Nordrhein-Westfalen
Germany	Local Institution - 0128	Düsseldorf	Nordrhein-Westfalen
Germany	Local Institution - 0007	Hamburg
Germany	Local Institution - 0076	Kempten	Bayern
Germany	Local Institution - 0055	Leipzig	Sachsen
Germany	Local Institution - 0059	Munich	Bayern
Germany	Local Institution - 0028	Mutlangen
Greece	Local Institution - 0127	Alexandroupolis
Greece	Attikon General University Hospital	Chaidari	Attikí
Greece	Local Institution - 0129	Thessaloniki	Thessaloníki
Hong Kong	Local Institution - 0178	Hksar
Hong Kong	Local Institution - 0180	Shatin
Italy	IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola	Bologna
Italy	Local Institution - 0075	Firenze	Toscana
Italy	Local Institution - 0088	Milano	Lombardia
Italy	Local Institution - 0089	Padova	Veneto
Italy	Local Institution - 0067	Pavia
Italy	Local Institution - 0053	Reggio Calabria
Italy	Local Institution - 0143	Roma
Italy	Fondazione Policlinico Tor Vergata	Rome	Lazio
Italy	Local Institution - 0052	Rozzano	Milano
Japan	Local Institution - 0153	Amagasaki	Hyogo
Japan	Local Institution - 0185	Fukuyama	Hiroshima
Japan	Local Institution - 0184	Higashiibaraki	Ibaraki
Japan	Local Institution - 0188	Hitachi	Ibaraki
Japan	Local Institution - 0181	Itabashiku	Tokyo
Japan	Local Institution - 0187	Kitakyushu	Fukuoka
Japan	Japan Community Healthcare Organization Kyushu Hospital	Kitakyushu-shi	Fukuoka
Japan	Local Institution - 0186	Maebashi	Gunma
Japan	Local Institution - 0183	Matsuyama	Ehime
Japan	Local Institution - 0182	Ogaki	Gifu
Japan	Osaka Metropolitan University Hospital	Osaka
Japan	Local Institution - 0130	Sagamihara	Kanagawa
Japan	Aiiku Hospital	Sapporo	Hokkaido
Japan	Local Institution - 0135	Sendai-shi	Miyagi
Japan	Local Institution - 0150	Shinagawa-ku	Tokyo
Korea, Republic of	Local Institution - 0058	Hwasun Gun	Jeonranamdo
Korea, Republic of	Local Institution - 0051	Jung-gu	Taegu-Kwangyokshi
Korea, Republic of	Local Institution - 0012	Seoul	Seoul-teukbyeolsi [Seoul]
Korea, Republic of	Local Institution - 0036	Seoul	Seoul-teukbyeolsi [Seoul]
Korea, Republic of	Local Institution - 0048	Seoul	Seoul Teugbyeolsi
Poland	Local Institution - 0043	Katowice
Poland	Local Institution - 0097	Olsztyn	Warminsko-mazurskie
Poland	Local Institution - 0044	Wroclaw	Dolnoslaskie
Spain	Local Institution - 0105	Barcelona	Barcelona [Barcelona]
Spain	Local Institution - 0107	Granada
Spain	Local Institution - 0106	L'Hospitalet de Llobregat	Catalunya [Cataluña]
Spain	Local Institution - 0111	Madrid
Spain	Local Institution - 0112	Orense
Spain	Local Institution - 0110	Oviedo
Spain	Local Institution - 0108	Salamanca
Spain	Local Institution - 0109	Valencia	Valenciana, Comunitat
Sweden	Local Institution - 0113	Gothenburg	Västra Götalands Län [se-14]
Sweden	Local Institution - 0117	Lund	Skåne Län [se-12]
Sweden	Local Institution - 0119	Örebro	Örebro Län [se-18]
Sweden	Local Institution - 0118	Stockholm	Stockholms Län [se-01]
Switzerland	Local Institution - 0066	Basel
Switzerland	Local Institution - 0077	st.Gallen	Sankt Gallen
Turkey	Local Institution - 0138	Izmir
Turkey	Local Institution - 0139	Pendik	Istanbul
Turkey	Local Institution - 0140	Samsun
United States	Charleston Oncology, P.A.	Charleston	South Carolina
United States	Novant Health Presbyterian Medical Center	Charlotte	North Carolina
United States	Local Institution - 0174	Detroit	Michigan
United States	Hematology-Oncology Associates of Central New York, PC	East Syracuse	New York
United States	Inova Schar Cancer Institute	Fairfax	Virginia
United States	Houston Methodist Hospital	Houston	Texas
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Local Institution - 0173	Louisville	Kentucky
United States	University of Miami Hospital and Clinics, Sylvester Cancer Center	Miami	Florida
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	AHN West Penn Hospital	Pittsburgh	Pennsylvania
United States	Local Institution - 0096	Portland	Oregon
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	Advanced Research	Tamarac	Florida
United States	Local Institution - 0095	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Canada,  China,  Czechia,  Denmark,  France,  Germany,  Greece,  Hong Kong,  Italy,  Japan,  Korea, Republic of,  Poland,  Spain,  Sweden,  Switzerland,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with Adverse Events (AEs) evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria v.5.0	Phase 2	6 cycles plus 28 days (up to 24 weeks)
Primary	Number of participants who achieved complete remission (CR) per International Working Group (IWG) 2006 criteria within 6 cycles	Phase 2 and 3	Up to 24 weeks
Secondary	Number of participants who achieved Overall Response (OR) per IWG 2006 criteria within 6 cycles	Phase 2 and Phase 3; Overall Response is defined as complete response (CR), partial remission (PR), marrow complete response (mCR), hematologic improvement-erythroid response (HI-E), hematologic improvement-platelet response (HI-P), or hematologic improvement-neutrophil response (HI-N) as per IWG 2006 criteria	Up to 24 weeks
Secondary	Number of participants who achieved 84-day packed red blood cells transfusion independence (pRBC-TI)	Phase 2 and Phase 3	Up to 32 weeks
Secondary	pRBC-TI duration	Phase 2 and Phase 3	Over the course of the study, an average of 1 year
Secondary	Number of participants who achieve 84 day platelet transfusion independence (PLT-TI) within 6 cycles	Phase 2 and Phase 3	Over the course of the study, an average of 1 year
Secondary	PLT-TI duration	Phase 2 and Phase 3	Over the course of the study, an average of 1 year
Secondary	Number of participants who achieved pRBC transfusion reduction	Phase 3	Over the course of the study, an average of 1 year
Secondary	pRBC transfusion reduction duration	Phase 3	Over the course of the study, an average of 1 year
Secondary	CR duration	Phase 2 and Phase 3	Over the course of the study, an average of 1 year
Secondary	Best OR	Phase 2 and Phase 3	Over the course of the study, an average of 1 year
Secondary	OR duration	Phase 2 and Phase 3	Over the course of the study, an average of 1 year
Secondary	Overall Survival (OS)	Phase 3	Up to 5 years after discontinuation of Investigational Product, approximately 6 years
Secondary	Event-free Survival (EFS)	Phase 3	Up to 5 years after discontinuation of Investigational Product, approximately 6 years
Secondary	Time to acute myeloid leukemia (AML)	Phase 3	Up to 5 years after discontinuation of Investigational Product, approximately 6 years
Secondary	Time to subsequent therapy	Phase 3	Up to 5 years after discontinuation of Investigational Product, approximately 6 years
Secondary	Iron parameters measured from blood	Phase 3	Over the course of the study, an average of 1 year
Secondary	Number of participants with Adverse Events (AEs) evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria v.5.0	Phase 3	Up to end of treatment/early termination, an average of 1 year
Secondary	Summary statistics for Functional Assessment of Cancer Therapy-Anemia (FACT-An) scales and subscales at each assessment point for each treatment arm	Phase 3	Up to end of treatment/early termination, an average of 1 year
Secondary	Summary statistics for Quality of Life in Myelodysplasia Scale (QUALMS) scales and subscales at each assessment point for each treatment arm	Phase 3	Up to end of treatment/early termination, an average of 1 year
Secondary	Summary statistics for the EuroQol 5 Dimension 5 Level (EQ-5D-5L) scales and subscales at each assessment point for each treatment arm	Phase 3	Up to end of treatment/early termination, an average of 1 year
Secondary	Number of participants with healthcare resource use associated with the investigational product (IP)	Phase 3	Over the course of the study, an average of 1 year

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting