Clinical trial NCT05469737: 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)
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Myelodysplastic Syndromes
Keywords: Anemia
Thrombocytopenia
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2022-07-22
Enrollment: 230
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 6 cycles plus 28 days (up to 24 weeks)
measure: Number of participants who achieved complete remission (CR) per International Working Group (IWG) 2006 criteria within 6 cycles
timeFrame: Up to 24 weeks
Secondary outcomes:
measure: Number of participants who achieved Overall Response (OR) per IWG 2006 criteria within 6 cycles
timeFrame: Up to 24 weeks
measure: Number of participants who achieved 84-day packed red blood cells transfusion independence (pRBC-TI)
timeFrame: Up to 32 weeks
measure: pRBC-TI duration
timeFrame: Over the course of the study, an average of 1 year
measure: Number of participants who achieve 84 day platelet transfusion independence (PLT-TI) within 6 cycles
timeFrame: Over the course of the study, an average of 1 year
measure: PLT-TI duration
timeFrame: Over the course of the study, an average of 1 year
measure: Number of participants who achieved pRBC transfusion reduction
timeFrame: Over the course of the study, an average of 1 year
measure: pRBC transfusion reduction duration
timeFrame: Over the course of the study, an average of 1 year
measure: CR duration
timeFrame: Over the course of the study, an average of 1 year
measure: Best OR
timeFrame: Over the course of the study, an average of 1 year
measure: OR duration
timeFrame: Over the course of the study, an average of 1 year
measure: Overall Survival (OS)
timeFrame: Up to 5 years after discontinuation of Investigational Product, approximately 6 years
measure: Event-free Survival (EFS)
timeFrame: Up to 5 years after discontinuation of Investigational Product, approximately 6 years
measure: Time to acute myeloid leukemia (AML)
timeFrame: Up to 5 years after discontinuation of Investigational Product, approximately 6 years
measure: Time to subsequent therapy
timeFrame: Up to 5 years after discontinuation of Investigational Product, approximately 6 years
measure: Iron parameters measured from blood
timeFrame: Over the course of the study, an average of 1 year
measure: 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
timeFrame: Up to end of treatment/early termination, an average of 1 year
measure: Summary statistics for Functional Assessment of Cancer Therapy-Anemia (FACT-An) scales and subscales at each assessment point for each treatment arm
timeFrame: Up to end of treatment/early termination, an average of 1 year
measure: Summary statistics for Quality of Life in Myelodysplasia Scale (QUALMS) scales and subscales at each assessment point for each treatment arm
timeFrame: Up to end of treatment/early termination, an average of 1 year
measure: Summary statistics for the EuroQol 5 Dimension 5 Level (EQ-5D-5L) scales and subscales at each assessment point for each treatment arm
timeFrame: Up to end of treatment/early termination, an average of 1 year
measure: Number of participants with healthcare resource use associated with the investigational product (IP)
timeFrame: Over the course of the study, an average of 1 year
Other outcomes:
Locations:
city: Miami
country: United States
facility: Local Institution - 0137
state: Florida
city: Tamarac
country: United States
facility: Local Institution - 0147
state: Florida
city: East Syracuse
country: United States
facility: Local Institution - 0132
state: New York
city: Pittsburgh
country: United States
facility: Local Institution - 0073
state: Pennsylvania
city: Houston
country: United States
facility: Local Institution - 0014
state: Texas
city: Houston
country: United States
facility: Local Institution - 0086
state: Texas
city: Fairfax
country: United States
facility: Local Institution - 0123
state: Virginia
city: Pilar
country: Argentina
facility: Local Institution - 0070
state: Buenos Aires
city: ABB
country: Argentina
facility: Local Institution - 0039
state: Ciudad Autónoma De Buenos Aires
city: Buenos Aires
country: Argentina
facility: Local Institution - 0016
city: Buenos Aires
country: Argentina
facility: Local Institution - 0022
city: Buenos Aires
country: Argentina
facility: Local Institution - 0050
city: Clayton
country: Australia
facility: Local Institution - 0006
state: Victoria
city: Melbourne
country: Australia
facility: Local Institution - 0018
state: Victoria
city: Melbourne
country: Australia
facility: Local Institution - 0004
state: Victoria
city: Melbourne
country: Australia
facility: Local Institution - 0003
city: Toronto
country: Canada
facility: Local Institution - 0008
state: Ontario
city: Toronto
country: Canada
facility: Local Institution - 0015
state: Ontario
city: Montréal
country: Canada
facility: Local Institution - 0090
state: Quebec
city: Wuhan
country: China
facility: Local Institution - 0156
state: Hubei
city: Hradec Kralove
country: Czechia
facility: Local Institution - 0060
city: Aarhus
country: Denmark
facility: Local Institution - 0115
state: Midtjylland
city: Aalborg
country: Denmark
facility: Local Institution - 0116
state: Nordjylland
city: Pessac
country: France
facility: Local Institution - 0063
state: Aquitaine
city: Tours
country: France
facility: Local Institution - 0024
state: Indre-et-Loire
city: Angers
country: France
facility: Local Institution - 0094
state: Maine-et-Loire
city: Lille
country: France
facility: Local Institution - 0056
state: Nord
city: Villejuif
country: France
facility: Local Institution - 0085
state: Val-de-Marne
city: Paris
country: France
facility: Local Institution - 0082
city: Duisburg
country: Germany
facility: Local Institution - 0081
state: Nordrhein-Westfalen
city: Düsseldorf
country: Germany
facility: Local Institution - 0128
state: Nordrhein-Westfalen
city: Leipzig
country: Germany
facility: Local Institution - 0055
state: Sachsen
city: Dresden
country: Germany
facility: Local Institution - 0037
city: Hamburg
country: Germany
facility: Local Institution - 0007
city: Mutlangen
country: Germany
facility: Local Institution - 0028
city: Chaidari
country: Greece
facility: Local Institution - 0125
state: Attikí
city: Thessaloniki
country: Greece
facility: Local Institution - 0129
state: Thessaloníki
city: Alexandroupolis
country: Greece
facility: Local Institution - 0127
city: Hksar
country: Hong Kong
facility: Local Institution - 0178
city: Shatin
country: Hong Kong
facility: Local Institution - 0180
city: Rome
country: Italy
facility: Local Institution - 0061
state: Lazio
city: Rozzano
country: Italy
facility: Local Institution - 0052
state: Milano
city: Firenze
country: Italy
facility: Local Institution - 0075
state: Toscana
city: Bologna
country: Italy
facility: Local Institution - 0101
city: Kitakyushu-shi
country: Japan
facility: Local Institution - 0136
state: Fukuoka
city: Sapporo
country: Japan
facility: Local Institution - 0154
state: Hokkaido
city: Amagasaki
country: Japan
facility: Local Institution - 0153
state: Hyogo
city: Sagamihara
country: Japan
facility: Local Institution - 0130
state: Kanagawa
city: Sendai-shi
country: Japan
facility: Local Institution - 0135
state: Miyagi
city: Shinagawa-ku
country: Japan
facility: Local Institution - 0150
state: Tokyo
city: Osaka
country: Japan
facility: Local Institution - 0124
city: Hwasun Gun
country: Korea, Republic of
facility: Local Institution - 0058
state: Jeonranamdo
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0048
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0036
state: Seoul-teukbyeolsi [Seoul]
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0012
state: Seoul-teukbyeolsi [Seoul]
city: Jung-gu
country: Korea, Republic of
facility: Local Institution - 0051
state: Taegu-Kwangyǒkshi
city: Olsztyn
country: Poland
facility: Local Institution - 0097
state: Warmińsko-mazurskie
city: Valencia
country: Spain
facility: Local Institution - 0109
state: Valenciana, Comunitat
city: Granada
country: Spain
facility: Local Institution - 0107
city: Madrid
country: Spain
facility: Local Institution - 0111
city: Orense
country: Spain
facility: Local Institution - 0112
city: Oviedo
country: Spain
facility: Local Institution - 0110
city: Salamanca
country: Spain
facility: Local Institution - 0108
city: Stockholm
country: Sweden
facility: Local Institution - 0118
state: Stockholms Län [se-01]
city: Örebro
country: Sweden
facility: Local Institution - 0119
state: Örebro Län [se-18]
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: