Clinical Trials /

SY-1425 Plus Azacitidine in Participants With Newly Diagnosed RARA-positive Higher-Risk Myelodysplastic Syndrome

NCT04797780

Description:

This study compares the efficacy of SY-1425 in combination with azacitidine to azacitidine in combination with placebo in participants who are Retinoic Acid Receptor Alpha (RARA) positive, and newly diagnosed with higher-risk myelodysplastic syndrome (MDS), and who have not received treatment for this diagnosis. The primary goal of the study is to compare the complete remission rate between the two treatment arms.

Related Conditions:
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: SY-1425 Plus Azacitidine in Participants With Newly Diagnosed RARA-positive Higher-Risk Myelodysplastic Syndrome
  • Official Title: A Randomized, Double-blind, Placebo-controlled Phase 3 Study of SY-1425 Plus Azacitidine Versus Placebo Plus Azacitidine in Newly Diagnosed, RARA-positive Adult Patients With Higher-risk Myelodysplastic Syndrome

Clinical Trial IDs

  • ORG STUDY ID: SY-1425-301
  • SECONDARY ID: 2020-004528-40
  • NCT ID: NCT04797780

Conditions

  • Myelodysplastic Syndromes

Interventions

DrugSynonymsArms
SY-1425 + AzacitidineTamibaroteneSY-1425 + Azacitidine
SY-1425 Matched Placebo + AzacitidineSY-1425 Matched Placebo + Azacitidine

Purpose

This study compares the efficacy of SY-1425 in combination with azacitidine to azacitidine in combination with placebo in participants who are Retinoic Acid Receptor Alpha (RARA) positive, and newly diagnosed with higher-risk myelodysplastic syndrome (MDS), and who have not received treatment for this diagnosis. The primary goal of the study is to compare the complete remission rate between the two treatment arms.

Detailed Description

      A subset of participants have MDS characterized by an overexpression of the RARA gene. A
      blood test will be used to identify participants with RARA-positive MDS. Assessment of the
      RARA biomarker for study eligibility will be done by collection of blood samples from
      potential study participants at the pre-screening visit and testing at a central laboratory.
      Participants who meet eligibility requirements will be randomized 2:1 to receive either
      SY-1425 plus azacitidine or placebo plus azacitidine.
    

Trial Arms

NameTypeDescriptionInterventions
SY-1425 + AzacitidineExperimentalSY-1425: 6 mg administered orally twice per day (BID) on Days 8 through 28 of each 28-day treatment cycle. Azacitidine: 75 mg/m^2 administered intravenously or subcutaneously each day on Days 1 through 7 of each 28-day treatment cycle.
  • SY-1425 + Azacitidine
SY-1425 Matched Placebo + AzacitidinePlacebo ComparatorPlacebo: SY-1425-matching tablets administered orally BID on Days 8 through 28 of each 28-day treatment cycle. Azacitidine: 75 mg/m^2 administered intravenously or subcutaneously each day on Days 1 through 7 of each 28-day treatment cycle.
  • SY-1425 Matched Placebo + Azacitidine

Eligibility Criteria

        Key Inclusion Criteria:

          1. Participants must be at least 18 years old at the time of signing of an informed
             consent.

          2. Participants must be RARA-positive based on the investigational assay.

          3. Participants must be newly diagnosed with HR-MDS as follows:

             Diagnosis of MDS according to the World Health Organization (WHO) classification
             (Arber 2016) and classified by the Revised International Prognostic Scoring System
             (IPSS R) risk category as very high, high, or intermediate risk.

          4. Participants must have Eastern Cooperative Oncology Group (ECOG) Performance Status of
             ≤2.

        Key Exclusion Criteria:

          1. Participants are suitable for and agree to undergo allogeneic HSCT at the time of
             Screening.

          2. Participants who received prior treatment for MDS with any hypomethylating agent,
             chemotherapy or allogeneic HSCT.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Proportion of Participants with Complete Remission
Time Frame:Up to 5 Years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Proportion of Participants Who Achieve Objective Response
Time Frame:Up to 5 Years
Safety Issue:
Description:
Measure:Duration of Event Free Survival
Time Frame:Up to 5 Years
Safety Issue:
Description:
Measure:Duration of Overall Survival
Time Frame:Up to 5 Years
Safety Issue:
Description:
Measure:Proportion of Participants Who Achieve Transfusion Independence
Time Frame:Up to 5 Years
Safety Issue:
Description:
Measure:Duration of Complete Response
Time Frame:Up to 5 Years
Safety Issue:
Description:
Measure:Duration of Overall Response
Time Frame:Up to 5 Years
Safety Issue:
Description:
Measure:Time to Complete Remission
Time Frame:Up to 5 Years
Safety Issue:
Description:
Measure:Time to Initial Response
Time Frame:Up to 5 Years
Safety Issue:
Description:
Measure:Proportion of participants with Adverse Events and Serious Adverse Events
Time Frame:Up to 5 Years
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Syros Pharmaceuticals

Trial Keywords

  • Higher-Risk
  • Retinoic Acid Receptor Alpha (RARA) positive
  • Newly Diagnosed
  • Myelodysplastic Syndromes

Last Updated

March 15, 2021