NCT04797780

Brief Summary

This study compares the efficacy of Tamibarotene 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 (HR-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.

Trial Health

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Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
246

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Feb 2021

Typical duration for phase_3

Geographic Reach
13 countries

128 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 8, 2021

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

March 11, 2021

Completed
4 days until next milestone

First Posted

Study publicly available on registry

March 15, 2021

Completed
3.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 13, 2024

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 13, 2024

Completed
5 months until next milestone

Results Posted

Study results publicly available

April 10, 2025

Completed
Last Updated

April 10, 2025

Status Verified

April 1, 2025

Enrollment Period

3.8 years

First QC Date

March 11, 2021

Results QC Date

January 2, 2025

Last Update Submit

April 7, 2025

Conditions

Keywords

Higher-RiskRetinoic Acid Receptor Alpha (RARA) positiveNewly DiagnosedMyelodysplastic Syndromes

Outcome Measures

Primary Outcomes (1)

  • Percentage of Participants With Complete Remission (CR)

    CR was determined by the investigator per the modified International Working Group Myelodysplastic Syndrome (IWG MDS). CR was defined as participants with hemoglobin ≥11 grams/deciliter (g/dL), neutrophils ≥1.0\*10\^9/L, platelets ≥100\*10\^9/L, blasts 0%, bone marrow blasts (BMBs) ≤5% and normal maturation of all cell lines, persistent dysplasia were noted.

    Up to 45 months

Secondary Outcomes (9)

  • Duration of Overall Response (DOR)

    Up to 45 months

  • Number of Participants Who Achieved Transfusion Independence (TI)

    Up to 45 months

  • Percentage of Participants Who Achieved Overall Response (OR)

    Up to 45 months

  • Duration of Complete Response (DOCR)

    Up to 45 months

  • Time to Complete Remission (TCR)

    Up to 45 months

  • +4 more secondary outcomes

Study Arms (2)

Tamibarotene + Azacitidine

EXPERIMENTAL

Tamibarotene: 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: TamibaroteneDrug: Azacitidine

Tamibarotene Matched Placebo + Azacitidine

PLACEBO COMPARATOR

Placebo: Tamibarotene-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: PlaceboDrug: Azacitidine

Interventions

Administered as specified in the treatment arm

Also known as: SY-1425
Tamibarotene + Azacitidine

Administered as specified in the treatment arm

Tamibarotene Matched Placebo + Azacitidine

Administered as specified in the treatment arm

Tamibarotene + AzacitidineTamibarotene Matched Placebo + Azacitidine

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Participants must be RARA-positive based on the investigational assay.
  • Participants must be newly diagnosed with HR-MDS as follows:
  • Diagnosis of MDS according to the World Health Organization (WHO) classification and classified by the Revised International Prognostic Scoring System (IPSS R) risk category as very high, high, or intermediate risk.
  • Participants must have Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤2.

You may not qualify if:

  • Participants are suitable for and agree to undergo allogeneic hematopoietic stem cell transplant (HSCT) at the time of screening.
  • Participants who need treatment prior to stem cell transplant can receive treatment on this study and stop the study treatment when they are ready to proceed to transplant.
  • Participants who received prior treatment for MDS with any hypomethylating agent, lenalidomide, chemotherapy or allogeneic HSCT.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (128)

University of Arizona

Tucson, Arizona, 85719, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

University of California, Los Angelas

Los Angeles, California, 90095, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06510, United States

Location

Comprehensive Hematology and Oncology

St. Petersburg, Florida, 33709, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University of Illinois Cancer Center

Chicago, Illinois, 60612, United States

Location

Orchard Healthcare Research Inc.

Skokie, Illinois, 60077, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Tulane Cancer Center

New Orleans, Louisiana, 70112, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

American Oncology Partners of Maryland, PA

Bethesda, Maryland, 20817, United States

Location

Morristown Medical Center- Atlantic Hematology Oncology

Morristown, New Jersey, 02140, United States

Location

Northwell Health

Lake Success, New York, 11042, United States

Location

Novant Health Inc

Charlotte, North Carolina, 28204, United States

Location

Novant Health Cancer Institute - Forsyth

Winston-Salem, North Carolina, 27103, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

TriStar - Sarah Cannon BMT

Nashville, Tennessee, 37203, United States

Location

University of Utah Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

Medical University of Graz

Graz, 8036, Austria

Location

Salzburg Cancer Research Institute (SCRI)

Salzburg, 5020, Austria

Location

Klinik Hietzing

Vienna, Austria

Location

ZNA Middelheim

Antwerp, Belgium

Location

Institut Jules Bordet

Brussels, Belgium

Location

Ghent University Hospital

Ghent, Belgium

Location

Hospital De Jolimont

La Louvière, 7100, Belgium

Location

CHU de Liège

Liège, Belgium

Location

AZ Delta

Roeselare, 8800, Belgium

Location

CHU-UCL Namur

Yvoir, 5530, Belgium

Location

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Location

Juravinski Cancer Centre

Hamilton, Ontario, ON L8V 1C3, Canada

Location

London Health Sciences Center

London, Ontario, N6A 5W9, Canada

Location

Princess Margaret Cancer Centre - University Health Network

Toronto, Ontario, Canada

Location

McGill University Health Centre (MUHC)

Montreal, Quebec, H4A 3J1, Canada

Location

Tom Baker Cancer Centre

Calgary, Canada

Location

London Health Sciences Centre

London, ON, Canada

Location

Fakultni nemocnice Olomouc (University Hospital Olomouc)

Olomouc, Czechia

Location

University Hospital Ostrava

Ostrava, Czechia

Location

General University Hospital Prague

Prague, Czechia

Location

CHU Amiens-Picardie

Amiens, 80054, France

Location

CHU d'Angers

Angers, 49933, France

Location

Centre Hospitalier de la Côte Basque Hématologie Clinique

Bayonne, 64109, France

Location

Hôpital Avicenne

Bobigny, 93000, France

Location

CHRU de BREST - Hôpital Morvan

Brest, 29200, France

Location

CHU Clermont Ferrand / CHU Estaing

Clermont-Ferrand, France

Location

CHU Grenoble Alpes Hôpital Nord Michallon

La Tronche, France

Location

Hopital Mignot

Le Chesnay, 78150, France

Location

CHU de Limoges

Limoges, 87000, France

Location

Centre Léon Bérard

Lyon, 69373, France

Location

CHU la Conception

Marseille, France

Location

CHU Nantes - Hotel Dieu

Nantes, 44093, France

Location

CHU de Nice - Hopital L'Archet

Nice, 06200, France

Location

Hôpital Saint Louis

Paris, 75475, France

Location

CHU Bordeaux

Pessac, 33604, France

Location

CHU Lyon Sud

Pierre-Bénite, 69495, France

Location

CHU Poiters

Poitiers, 86021, France

Location

CHU Saint Etienne

Saint-Priest-en-Jarez, France

Location

ICANS Strasbourg

Strasbourg, 67033, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Universitätsklinikum Augsburg

Augsburg, Germany

Location

Helios Klinikum Berlin Buch GmbH

Berlin, Germany

Location

Universitätsklinikum Freiburg

Freiburg im Breisgau, Germany

Location

Universitätsmedizin Göttingen

Göttingen, Germany

Location

Universitätsklinikum Halle (Saale)

Halle, Germany

Location

Universitätsklinikum Marburg

Marburg, Germany

Location

Universitätsklinikum Münster

Münster, Germany

Location

Semmelweis Egyetem

Budapest, 1083, Hungary

Location

Debrecen University Medical and Health Science Centre

Debrecen, H-4012, Hungary

Location

Markhot Ferenc Oktatókórház és Rendelőintézet, Belgyógyászati- és Infektológiai Centrum

Eger, Hungary

Location

Petz Aladar County Teaching Hospital

Győr, Hungary

Location

Josa Andras Teaching Hospital

Nyíregyháza, 4400, Hungary

Location

Barzilai Medical Center of Ashkelon

Ashkelon, Israel

Location

Bnai Zion Medical center

Haifa, 31048, Israel

Location

Shaare Zedek Medical Center

Jerusalem, 9103102, Israel

Location

Sheba Medical Center

Ramat Gan, Israel

Location

Kaplan Medical Center

Rehovot, 7661041, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, Israel

Location

IRCCS Azienda Ospedaliero-Universitaria di Bologna

Bologna, 40138, Italy

Location

ASST Spedali Civili di Brescia

Brescia, Italy

Location

Azienda Ospedaliero-Universitaria di Ferrara

Ferrara, 44124, Italy

Location

AOU Careggi

Florence, Italy

Location

Ospedale Policlinico San Martino

Genova, 16132, Italy

Location

Romagnolo Institute to Study Tumors "Dino Amadori "/ Meldona

Meldola, 47014, Italy

Location

A.O.U. Maggiore della Carità

Novara, 28100, Italy

Location

Ospedali Marche Nord Centro Ematologia e Trapianti

Pesaro, 61122, Italy

Location

Ospedale S.Maria delle Croci

Ravenna, Italy

Location

Ospedale S. Eugenio - ASL Roma 2

Roma, Italy

Location

Fondazione Policlinico Tor Vergata

Rome, 00133, Italy

Location

AOUI di Verona

Verona, Italy

Location

University Clinic Gdansk

Gdansk, 80-952, Poland

Location

Pomeranian Hospital Gdynia

Gdynia, 81-519, Poland

Location

Wojewodzki Szpital Specjalistyczny w Legnicy

Legnica, 59-220, Poland

Location

Instytut Hematologii i Transfuzjologii, Klinika Hematologii

Warsaw, Poland

Location

University Clinic Warsaw

Warsaw, Poland

Location

Alfred Sokołowski Hospital Wałbrzych

Wałbrzych, Poland

Location

Institut Catala d'Oncologia - Hospital Duran i Reynals Location

Badalona, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

H. Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

Fundación Privada Instituto de Investigación Oncológica Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

Hospital del Mar Secretaria d'Hematologia Clínica

Barcelona, Spain

Location

Hospital Universitario de Burgos

Burgos, 09006, Spain

Location

Hospital San Pedro de Alcántara

Cáceres, Spain

Location

MD Anderson Cancer Center

Madrid, 28033, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

H. Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario de La Princesa

Madrid, Spain

Location

Hospital General Universitario J.M. Morales Meseguer

Murcia, Spain

Location

Hospital Universitario Central de Asturia

Oviedo, 33011, Spain

Location

Hospital Son Llatzer

Palma de Mallorca, 07198, Spain

Location

Clinica Universidad Navarra

Pamplona, 31008, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario Donostia

San Sebastián, Spain

Location

Hospital Universitario Marqués de Valdecilla

Santander, 39008, Spain

Location

Hospital Universitario Virgen Del Rocio

Seville, 41013, Spain

Location

Hospital Universitario y Politécnico La Fe

Valencia, 46026, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, Spain

Location

Castle Hill Hospital, Cottingham

Cottingham, United Kingdom

Location

Ninewells Hospital

Dundee, United Kingdom

Location

Western General Hospital in NHS Lothian Edinburgh Scotland

Edinburgh, United Kingdom

Location

Clatterbridge Cancer Centre NHS Foundation Trust

Liverpool, United Kingdom

Location

King's College Hospital NHS Foundation Trust

London, United Kingdom

Location

The Royal Marsden Foundation Trust

London, United Kingdom

Location

University Hospital Southampton NHS Foundation Trust

Southampton, United Kingdom

Location

Sandwell and West Birmingham Hospital NHS Trust

West Bromwich, United Kingdom

Location

Related Publications (2)

  • DeZern AE, Thepot S, de Botton S, Patriarca A, Deeren D, Torregrossa-Diaz JM, Marconi G, Bernal T, Bergua Burgues J, Xicoy B, Jonasova A, Zeidan AM, Dimicoli-Salazar S, Simand C, Valcarcel D, Diez Campelo M, Chai-Ho W, Saini L, Garnier A, Geissler K, Ofran Y, Nagy Z, Krishnamurthy P, Lubbert M, Basak G, Carraway HE, Sallman DA, Borate U, Santini V, Campbell V, Fenaux P, Braun T, Lanza F, Zaucha JM, Roth DA, Paul S, Roy P, Kelly MJ, Volkert A, Chisholm J, Malak TA, Klimek VM, Cluzeau T. Pivotal results of SELECT-MDS-1 phase 3 study of tamibarotene with azacitidine in newly diagnosed higher-risk MDS. Blood Adv. 2025 Aug 26;9(16):4090-4099. doi: 10.1182/bloodadvances.2025016229.

  • Stahl M, DeZern AE. Is there a path forward for immunotherapy in patients with myelodysplastic syndromes? Lancet Haematol. 2024 Jan;11(1):e5-e7. doi: 10.1016/S2352-3026(23)00343-5. Epub 2023 Dec 5. No abstract available.

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

tamibaroteneAzacitidine

Condition Hierarchy (Ancestors)

Bone Marrow DiseasesHematologic DiseasesHemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza CompoundsOrganic ChemicalsCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsNucleosidesNucleic Acids, Nucleotides, and NucleosidesRibonucleosides

Limitations and Caveats

As per Sponsor decision, the study was terminated. Note that the study was terminated prior to the data from the questionnaires were collected, analyzed, summarized, or made available by the study sponsor.

Results Point of Contact

Title
Tiffany Crowell
Organization
Syros Pharmaceuticals

Study Officials

  • Medical Director

    Syros Pharmaceuticals Inc.

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 11, 2021

First Posted

March 15, 2021

Study Start

February 8, 2021

Primary Completion

November 13, 2024

Study Completion

November 13, 2024

Last Updated

April 10, 2025

Results First Posted

April 10, 2025

Record last verified: 2025-04

Data Sharing

IPD Sharing
Will not share

Locations