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: Active, not recruiting

Administrative data

• NCT number: NCT05469737
• Other study ID #: CA055-026
• Secondary ID: U1111-1276-5463
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: December 14, 2022
• Est. completion date: July 29, 2026

Study information

• Verified date: May 2024
• Source: Bristol-Myers Squibb
• Contact: n/a
• 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: Active, not 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	Local Institution - 0016	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 - 0003	Melbourne
Australia	Local Institution - 0004	Melbourne	Victoria
Australia	Local Institution - 0018	Melbourne	Victoria
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 - 0166	Shenyang	Liaoning
China	Local Institution - 0156	Wuhan	Hubei
Czechia	Local Institution - 0060	Hradec Kralove
Denmark	Local Institution - 0116	Aalborg	Nordjylland
Denmark	Local Institution - 0115	Aarhus	Midtjylland
France	Local Institution - 0094	Angers	Maine-et-Loire
France	Local Institution - 0056	Lille	Nord
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 - 0055	Leipzig	Sachsen
Germany	Local Institution - 0028	Mutlangen
Greece	Local Institution - 0127	Alexandroupolis
Greece	Local Institution - 0125	Chaidari	Attikí
Greece	Local Institution - 0129	Thessaloniki	Thessaloníki
Hong Kong	Local Institution - 0178	Hksar
Hong Kong	Local Institution - 0180	Shatin
Italy	Local Institution - 0101	Bologna
Italy	Local Institution - 0075	Firenze	Toscana
Italy	Local Institution - 0061	Rome	Lazio
Italy	Local Institution - 0052	Rozzano	Milano
Japan	Local Institution - 0153	Amagasaki	Hyogo
Japan	Local Institution - 0136	Kitakyushu-shi	Fukuoka
Japan	Local Institution - 0124	Osaka
Japan	Local Institution - 0130	Sagamihara	Kanagawa
Japan	Local Institution - 0154	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 - 0097	Olsztyn	Warminsko-mazurskie
Spain	Local Institution - 0107	Granada
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 - 0119	Örebro	Örebro Län [se-18]
Sweden	Local Institution - 0118	Stockholm	Stockholms Län [se-01]
United States	Local Institution - 0132	East Syracuse	New York
United States	Local Institution - 0123	Fairfax	Virginia
United States	Local Institution - 0014	Houston	Texas
United States	Local Institution - 0086	Houston	Texas
United States	Local Institution - 0137	Miami	Florida
United States	Local Institution - 0073	Pittsburgh	Pennsylvania
United States	Local Institution - 0147	Tamarac	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

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

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