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)
Study Details
Study Description
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).
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2/Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Part I - Oral-Aza (Dose 1)
|
Drug: Oral Azacitidine
Specified dose on specified days
Other Names:
|
Experimental: Part I - Oral-Aza (Dose 2)
|
Drug: Oral Azacitidine
Specified dose on specified days
Other Names:
|
Experimental: Part II - Oral-Aza (RP3D) RP3D: Recommended Phase 3 Dose |
Drug: Oral Azacitidine
Specified dose on specified days
Other Names:
|
Experimental: Part II - Placebo
|
Drug: Placebo for Oral Azacitidine
Specified dose on specified days
|
Outcome Measures
Primary Outcome Measures
- 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 [4 cycles plus 28 days (up to 20 weeks)]
Phase 2
- Number of participants who achieved First Overall Response (OR) [Up to 16 weeks]
Phase 2 First Overall Response is defined as modified complete response (modCR), 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 International Working Group (IWG) 2006 criteria
- Number of participants who achieved modified complete response (modCR) within 6 cycles [Up to 24 weeks]
Phase 3
Secondary Outcome Measures
- Number of participants who achieved modCR [Up to 24 weeks]
Phase 2
- Number of participants who achieved 56-day packed red blood cells-transfusion independence (pRBC-TI) as per IWG 2006 criteria [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 achieved platelet-transfusion independence (PLT-TI) as per IWG 2006 criteria [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
- modCR duration [Over the course of the study, an average of 1 year]
Phase 2 and Phase 3
- Number of participants who achieved OR within 6 cycles, defined as modCR, PR, mCR, HI-E, HI-P, HI-N as per IWG 2006 criteria [Up to 24 weeks]
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
- 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
- Time to acute myeloid leukemia (AML) [Up to 5 years after discontinuation of Investigational Product, approximately 6 years]
Phase 3
- Time to subsequent therapy [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
- 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
- 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
Eligibility Criteria
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 17 of low- or intermediate-risk disease (IPSS-R score between 1.5 and 4.5)
-
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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Local Institution - 0070 | Pilar | Buenos Aires | Argentina | 1629 |
2 | Local Institution - 0050 | Buenos Aires | Argentina | CP1280AEB | |
3 | Local Institution - 0019 | La Plata | Argentina | 1900 | |
4 | Local Institution - 0003 | Melbourne | Victoria | Australia | 3004 |
5 | Local Institution - 0034 | Linz | Oberösterreich | Austria | 4020 |
6 | Local Institution - 0029 | Vienna | Wien | Austria | 1140 |
7 | Local Institution - 0074 | Salzburg | Austria | 5020 | |
8 | Local Institution - 0008 | Toronto | Ontario | Canada | M4N 3M5 |
9 | Local Institution - 0028 | Mutlangen | Baden-Württemberg | Germany | 73557 |
10 | Local Institution - 0081 | Duisburg | Nordrhein-Westfalen | Germany | 47166 |
11 | Local Institution - 0037 | Dresden | Sachsen | Germany | 01307 |
12 | Local Institution - 0055 | Leipzig | Sachsen | Germany | 04103 |
13 | Local Institution - 0007 | Hamburg | Germany | 22081 | |
14 | Local Institution - 0076 | Kempten | Germany | 87439 |
Sponsors and Collaborators
- Bristol-Myers Squibb
Investigators
- Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb
Study Documents (Full-Text)
None provided.More Information
Additional Information:
- BMS Clinical Trial Information
- BMS Clinical Trial Patient Recruiting
- Investigator Inquiry Form
- FDA Safety Alerts and Recalls
Publications
None provided.- CA055-026
- U1111-1276-5463