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)
- Conditions
- Myelodysplastic Syndromes
- Interventions
- Registration Number
- NCT05469737
- Lead Sponsor
- Bristol-Myers Squibb
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 230
• 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part II - Oral-Aza (RP3D) Oral Azacitidine RP3D: Recommended Phase 3 Dose Part I - Oral-Aza (Dose 1) Oral Azacitidine - Part I - Oral-Aza (Dose 2) Oral Azacitidine - Part II - Placebo Placebo for Oral Azacitidine -
- Primary Outcome Measures
Name Time Method 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 6 cycles plus 28 days (up to 24 weeks) Phase 2
Number of participants who achieved complete remission (CR) per International Working Group (IWG) 2006 criteria within 6 cycles Up to 24 weeks Phase 2 and 3
- Secondary Outcome Measures
Name Time Method Best OR Over the course of the study, an average of 1 year Phase 2 and Phase 3
CR duration Over the course of the study, an average of 1 year Phase 2 and Phase 3
Number of participants who achieved Overall Response (OR) per IWG 2006 criteria within 6 cycles Up to 24 weeks 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 criteriaPLT-TI duration Over the course of the study, an average of 1 year Phase 2 and Phase 3
pRBC transfusion reduction duration Over the course of the study, an average of 1 year Phase 3
OR duration Over the course of the study, an average of 1 year Phase 2 and Phase 3
Event-free Survival (EFS) Up to 5 years after discontinuation of Investigational Product, approximately 6 years Phase 3
Number of participants who achieved 84-day packed red blood cells transfusion independence (pRBC-TI) Up to 32 weeks Phase 2 and Phase 3
Number of participants who achieved pRBC transfusion reduction Over the course of the study, an average of 1 year Phase 3
Time to acute myeloid leukemia (AML) Up to 5 years after discontinuation of Investigational Product, approximately 6 years Phase 3
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 Up to end of treatment/early termination, an average of 1 year Phase 3
Summary statistics for Quality of Life in Myelodysplasia Scale (QUALMS) scales and subscales at each assessment point for each treatment arm Up to end of treatment/early termination, an average of 1 year Phase 3
Summary statistics for the EuroQol 5 Dimension 5 Level (EQ-5D-5L) scales and subscales at each assessment point for each treatment arm Up to end of treatment/early termination, an average of 1 year Phase 3
pRBC-TI duration Over the course of the study, an average of 1 year Phase 2 and Phase 3
Number of participants who achieve 84 day platelet transfusion independence (PLT-TI) within 6 cycles Over the course of the study, an average of 1 year Phase 2 and Phase 3
Number of participants with healthcare resource use associated with the investigational product (IP) Over the course of the study, an average of 1 year Phase 3
Overall Survival (OS) Up to 5 years after discontinuation of Investigational Product, approximately 6 years Phase 3
Iron parameters measured from blood Over the course of the study, an average of 1 year Phase 3
Summary statistics for Functional Assessment of Cancer Therapy-Anemia (FACT-An) scales and subscales at each assessment point for each treatment arm Up to end of treatment/early termination, an average of 1 year Phase 3
Time to subsequent therapy Up to 5 years after discontinuation of Investigational Product, approximately 6 years Phase 3
Trial Locations
- Locations (65)
Local Institution - 0073
🇺🇸Pittsburgh, Pennsylvania, United States
Local Institution - 0180
🇭🇰Shatin, Hong Kong
Local Institution - 0154
🇯🇵Sapporo, Hokkaido, Japan
Local Institution - 0153
🇯🇵Amagasaki, Hyogo, Japan
Local Institution - 0085
🇫🇷Villejuif, Val-de-Marne, France
Local Institution - 0130
🇯🇵Sagamihara, Kanagawa, Japan
Local Institution - 0156
🇨🇳Wuhan, Hubei, China
Local Institution - 0132
🇺🇸East Syracuse, New York, United States
Local Institution - 0070
🇦🇷Pilar, Buenos Aires, Argentina
Local Institution - 0039
🇦🇷ABB, Ciudad Autónoma De Buenos Aires, Argentina
Local Institution - 0123
🇺🇸Fairfax, Virginia, United States
Local Institution - 0016
🇦🇷Buenos Aires, Argentina
Local Institution - 0022
🇦🇷Buenos Aires, Argentina
Local Institution - 0050
🇦🇷Buenos Aires, Argentina
Local Institution - 0006
🇦🇺Clayton, Victoria, Australia
Local Institution - 0004
🇦🇺Melbourne, Victoria, Australia
Local Institution - 0018
🇦🇺Melbourne, Victoria, Australia
Local Institution - 0003
🇦🇺Melbourne, Australia
Local Institution - 0090
🇨🇦Montréal, Quebec, Canada
Local Institution - 0008
🇨🇦Toronto, Ontario, Canada
Local Institution - 0015
🇨🇦Toronto, Ontario, Canada
Local Institution - 0115
🇩🇰Aarhus, Midtjylland, Denmark
Local Institution - 0060
🇨🇿Hradec Kralove, Czechia
Local Institution - 0116
🇩🇰Aalborg, Nordjylland, Denmark
Local Institution - 0094
🇫🇷Angers, Maine-et-Loire, France
Local Institution - 0063
🇫🇷Pessac, Aquitaine, France
Local Institution - 0024
🇫🇷Tours, Indre-et-Loire, France
Local Institution - 0082
🇫🇷Paris, France
Local Institution - 0056
🇫🇷Lille, Nord, France
Local Institution - 0128
🇩🇪Düsseldorf, Nordrhein-Westfalen, Germany
Local Institution - 0081
🇩🇪Duisburg, Nordrhein-Westfalen, Germany
Local Institution - 0037
🇩🇪Dresden, Germany
Local Institution - 0007
🇩🇪Hamburg, Germany
Local Institution - 0055
🇩🇪Leipzig, Sachsen, Germany
Local Institution - 0028
🇩🇪Mutlangen, Germany
Local Institution - 0125
🇬🇷Chaidari, Attikí, Greece
Local Institution - 0129
🇬🇷Thessaloniki, Thessaloníki, Greece
Local Institution - 0052
🇮🇹Rozzano, Milano, Italy
Local Institution - 0075
🇮🇹Firenze, Toscana, Italy
Local Institution - 0127
🇬🇷Alexandroupolis, Greece
Local Institution - 0178
🇭🇰Hksar, Hong Kong
Local Institution - 0061
🇮🇹Rome, Lazio, Italy
Local Institution - 0136
🇯🇵Kitakyushu-shi, Fukuoka, Japan
Local Institution - 0101
🇮🇹Bologna, Italy
Local Institution - 0135
🇯🇵Sendai-shi, Miyagi, Japan
Local Institution - 0150
🇯🇵Shinagawa-ku, Tokyo, Japan
Local Institution - 0124
🇯🇵Osaka, Japan
Local Institution - 0058
🇰🇷Hwasun Gun, Jeonranamdo, Korea, Republic of
Local Institution - 0036
🇰🇷Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of
Local Institution - 0012
🇰🇷Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of
Local Institution - 0097
🇵🇱Olsztyn, Warmińsko-mazurskie, Poland
Local Institution - 0051
🇰🇷Jung-gu, Taegu-Kwangyǒkshi, Korea, Republic of
Local Institution - 0109
🇪🇸Valencia, Valenciana, Comunitat, Spain
Local Institution - 0107
🇪🇸Granada, Spain
Local Institution - 0112
🇪🇸Orense, Spain
Local Institution - 0110
🇪🇸Oviedo, Spain
Local Institution - 0111
🇪🇸Madrid, Spain
Local Institution - 0108
🇪🇸Salamanca, Spain
Local Institution - 0118
🇸🇪Stockholm, Stockholms Län [se-01], Sweden
Local Institution - 0119
🇸🇪Örebro, Örebro Län [se-18], Sweden
Local Institution - 0147
🇺🇸Tamarac, Florida, United States
Local Institution - 0048
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Local Institution - 0137
🇺🇸Miami, Florida, United States
Local Institution - 0086
🇺🇸Houston, Texas, United States
Local Institution - 0014
🇺🇸Houston, Texas, United States