Myelodysplastic Syndromes
Conditions
Keywords
Anemia, Thrombocytopenia
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).
Interventions
DRUGOral Azacitidine
Specified dose on specified days
DRUGPlacebo for Oral Azacitidine
Specified dose on specified days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Iron parameters measured from blood | 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 |
| Event-free Survival (EFS) | Up to 5 years after discontinuation of Investigational Product, approximately 6 years | 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 criteria |
| Number of participants who achieved 84-day packed red blood cells transfusion independence (pRBC-TI) | Up to 32 weeks | Phase 2 and 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 |
| PLT-TI duration | Over the course of the study, an average of 1 year | 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 |
| pRBC transfusion reduction duration | Over the course of the study, an average of 1 year | Phase 3 |
| CR duration | Over the course of the study, an average of 1 year | Phase 2 and Phase 3 |
| Best OR | Over the course of the study, an average of 1 year | Phase 2 and Phase 3 |
| OR duration | Over the course of the study, an average of 1 year | Phase 2 and 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 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 |
| 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 |
| Time to acute myeloid leukemia (AML) | Up to 5 years after discontinuation of Investigational Product, approximately 6 years | 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 |
| Time to subsequent therapy | Up to 5 years after discontinuation of Investigational Product, approximately 6 years | Phase 3 |
Countries
Argentina, Australia, Canada, China, Czechia, Denmark, France, Germany, Greece, Hong Kong, Italy, Japan, Poland, South Korea, Spain, Sweden, United States
Contacts
STUDY_DIRECTORBristol-Myers Squibb
Bristol-Myers Squibb
Outcome results
None listed