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

Sponsor
Syros Pharmaceuticals (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04797780
Collaborator
(none)
190
Enrollment
42
Locations
2
Arms
96
Anticipated Duration (Months)
4.5
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or DiseaseIntervention/TreatmentPhase
  • Drug: SY-1425 + Azacitidine
  • Drug: SY-1425 Matched Placebo + Azacitidine
Phase 3

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
190 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Feb 8, 2021
Anticipated Primary Completion Date :
Jul 10, 2023
Anticipated Study Completion Date :
Feb 8, 2029

Arms and Interventions

ArmIntervention/Treatment
Experimental: SY-1425 + Azacitidine

SY-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.

Drug: SY-1425 + Azacitidine
SY-1425 will be administered at 6 mg twice per day (BID) (orally) each day on Days 8 through 28 of each 28-day treatment cycle (total daily dose of 12 mg). Azacitidine will be administered at 75 mg/m2 (intravenously or subcutaneously) each day on Days 1 through 7 of each 28-day treatment cycle. If dosing on Days 6 and 7 is not possible due to logistical limitations, these doses may be delayed to Days 8 and 9. SY-1425/placebo is permitted to overlap with azacitidine on Days 8 through 9 of this alternative schedule.
Other Names:
  • Tamibarotene
  • Placebo Comparator: SY-1425 Matched Placebo + Azacitidine

    Placebo: 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.

    Drug: SY-1425 Matched Placebo + Azacitidine
    SY-1425 matched placebo will be administered at twice per day (BID) (orally) each day on Days 8 through 28 of each 28-day treatment cycle. Azacitidine will be administered at 75 mg/m2 (intravenously or subcutaneously) each day on Days 1 through 7 of each 28-day treatment cycle. If dosing on Days 6 and 7 is not possible due to logistical limitations, these doses may be delayed to Days 8 and 9. SY-1425/placebo is permitted to overlap with azacitidine on Days 8 through 9 of this alternative schedule.

    Outcome Measures

    Primary Outcome Measures

    1. Proportion of Participants with Complete Remission [Up to 5 Years]

    Secondary Outcome Measures

    1. Proportion of Participants Who Achieve Objective Response [Up to 5 Years]

    2. Duration of Event Free Survival [Up to 5 Years]

    3. Duration of Overall Survival [Up to 5 Years]

    4. Proportion of Participants Who Achieve Transfusion Independence [Up to 5 Years]

    5. Duration of Complete Response [Up to 5 Years]

    6. Duration of Overall Response [Up to 5 Years]

    7. Time to Complete Remission [Up to 5 Years]

    8. Time to Initial Response [Up to 5 Years]

    9. Proportion of participants with Adverse Events and Serious Adverse Events [Up to 5 Years]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    1. 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.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1UC IrvineIrvineCaliforniaUnited States92697
    2University of Southern CaliforniaLos AngelesCaliforniaUnited States90033
    3University of California, Los AngelasLos AngelesCaliforniaUnited States90095
    4BRCR Medical Center, IncPlantationFloridaUnited States33322
    5Comprehensive Hematology and OncologySaint PetersburgFloridaUnited States33709
    6Piedmont Cancer InstituteAtlantaGeorgiaUnited States30318
    7University of IowaIowa CityIowaUnited States52242
    8Ochsner Clinic FoundationNew OrleansLouisianaUnited States70121
    9Johns Hopkins UniversityBaltimoreMarylandUnited States21287
    10American Oncology Partners of Maryland, PABethesdaMarylandUnited States20817
    11Orchard Healthcare Research Inc.WalthamMassachusettsUnited States02451
    12SCL Health Research Institute, Inc. (St. Vincent Frontier Cancer Center)BillingsMontanaUnited States59102
    13Montefiore Medical CenterBronxNew YorkUnited States11102
    14Cleveland ClinicClevelandOhioUnited States44195
    15University of Utah Huntsman Cancer InstituteSalt Lake CityUtahUnited States84112
    16Institut Jules BordetBrusselsBelgium
    17CHU de LiègeLiègeBelgium4000
    18CHU Amiens-PicardieAmiensFrance80054
    19CHU d'AngersAngersFrance49933
    20Centre Hospitalier de la Côte Basque Hématologie CliniqueBayonneFrance64109
    21Hôpital AvicenneBobignyFrance93000
    22CHRU de BREST - Hôpital MorvanBrestFrance29200
    23Hopital MignotLe ChesnayFrance78150
    24CHU Nantes - Hotel DieuNantesFrance44093
    25CHU de Nice - Hopital L'ArchetNiceFrance06200
    26Hôpital Saint LouisParisFrance75475
    27Centre Hospitalier de PerpignanPerpignanFrance66046
    28CHU BordeauxPessacFrance33604
    29CHU Lyon SudPierre-BéniteFrance69495
    30CHU PoitersPoitiersFrance86021
    31ICANS StrasbourgStrasbourgFrance67033
    32Institut Gustave RoussyVillejuifFrance94805
    33Romagnolo Institute to Study Tumors "Dino Amadori "/ MeldonaMeldolaItaly47014
    34Ospedale Infermi di RiminiRiminiItaly47923
    35Fundación Privada Instituto de Investigación Oncológica Vall d'HebronBarcelonaSpain08035
    36Hospital de la Santa Creu i Sant PauBarcelonaSpain08041
    37Hospital Universitario Fundacion Jimenez DiazMadridSpain28040
    38H. Universitario La PazMadridSpain28046
    39Hospital Universitario Central de AsturiaOviedoSpain33011
    40Hospital Son LlatzerPalma De MallorcaSpain07198
    41Clinica Universidad NavarraPamplonaSpain31008
    42Hospital Universitario de SalamancaSalamancaSpain37007

    Sponsors and Collaborators

    • Syros Pharmaceuticals

    Investigators

    • Study Director: Medical Director, MD, Syros Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Syros Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT04797780
    Other Study ID Numbers:
    • SY-1425-301
    • 2020-004528-40
    First Posted:
    Mar 15, 2021
    Last Update Posted:
    Nov 15, 2021
    Last Verified:
    Nov 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Syros Pharmaceuticals
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Nov 15, 2021