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)

Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Not yet recruiting
CT.gov ID
NCT05469737
Collaborator
(none)
250
14
4
99.1
17.9
0.2

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
  • Drug: Oral Azacitidine
  • Drug: Placebo for Oral Azacitidine
Phase 2/Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
250 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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)
Anticipated Study Start Date :
Sep 22, 2022
Anticipated Primary Completion Date :
Dec 23, 2025
Anticipated Study Completion Date :
Dec 24, 2030

Arms and Interventions

Arm Intervention/Treatment
Experimental: Part I - Oral-Aza (Dose 1)

Drug: Oral Azacitidine
Specified dose on specified days
Other Names:
  • BMS-986345
  • Oral-Aza
  • ONUREG®
  • Experimental: Part I - Oral-Aza (Dose 2)

    Drug: Oral Azacitidine
    Specified dose on specified days
    Other Names:
  • BMS-986345
  • Oral-Aza
  • ONUREG®
  • Experimental: Part II - Oral-Aza (RP3D)

    RP3D: Recommended Phase 3 Dose

    Drug: Oral Azacitidine
    Specified dose on specified days
    Other Names:
  • BMS-986345
  • Oral-Aza
  • ONUREG®
  • Experimental: Part II - Placebo

    Drug: Placebo for Oral Azacitidine
    Specified dose on specified days

    Outcome Measures

    Primary Outcome Measures

    1. 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

    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

    3. Number of participants who achieved modified complete response (modCR) within 6 cycles [Up to 24 weeks]

      Phase 3

    Secondary Outcome Measures

    1. Number of participants who achieved modCR [Up to 24 weeks]

      Phase 2

    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

    3. pRBC-TI duration [Over the course of the study, an average of 1 year]

      Phase 2 and Phase 3

    4. 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

    5. PLT-TI duration [Over the course of the study, an average of 1 year]

      Phase 2 and Phase 3

    6. Number of participants who achieved pRBC transfusion reduction [Over the course of the study, an average of 1 year]

      Phase 3

    7. pRBC transfusion reduction duration [Over the course of the study, an average of 1 year]

      Phase 3

    8. modCR duration [Over the course of the study, an average of 1 year]

      Phase 2 and Phase 3

    9. 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

    10. Best OR [Over the course of the study, an average of 1 year]

      Phase 2 and Phase 3

    11. OR duration [Over the course of the study, an average of 1 year]

      Phase 2 and Phase 3

    12. Overall Survival (OS) [Up to 5 years after discontinuation of Investigational Product, approximately 6 years]

      Phase 3

    13. Event-free Survival (EFS) [Up to 5 years after discontinuation of Investigational Product, approximately 6 years]

      Phase 3

    14. Time to acute myeloid leukemia (AML) [Up to 5 years after discontinuation of Investigational Product, approximately 6 years]

      Phase 3

    15. Time to subsequent therapy [Up to 5 years after discontinuation of Investigational Product, approximately 6 years]

      Phase 3

    16. Iron parameters measured from blood [Over the course of the study, an average of 1 year]

      Phase 3

    17. 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

    18. 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

    19. 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

    20. 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

    21. 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

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts 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 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:

    Publications

    None provided.
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT05469737
    Other Study ID Numbers:
    • CA055-026
    • U1111-1276-5463
    First Posted:
    Jul 22, 2022
    Last Update Posted:
    Aug 22, 2022
    Last Verified:
    Aug 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Bristol-Myers Squibb
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 22, 2022