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

Myelodysplastic Syndromes Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled Phase 3 Study of Tamibarotene Plus Azacitidine Versus Placebo Plus Azacitidine in Newly Diagnosed, Adult Patients Selected for RARA-positive Higher-risk Myelodysplastic Syndrome (SELECT MDS-1)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04797780
• Other study ID #: SY-1425-301
• Secondary ID: 2020-004528-40
• Status: Recruiting
• Phase: Phase 3
• Start date: February 8, 2021
• Est. completion date: February 8, 2029

Study information

• Verified date: March 2024
• Source: Syros Pharmaceuticals
• Contact: Clinical Trial Manager
• Phone: 617-674-9069
• Email: SELECTMDS1[@]syros.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 Tamibarotene plus azacitidine or placebo plus azacitidine.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 550
• Est. completion date: February 8, 2029
• Est. primary completion date: November 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• 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.

Key Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• Tamibarotene
Administered as specified in the treatment arm
• Placebo
Administered as specified in the treatment arm
• Azacitidine
Administered as specified in the treatment arm

Locations

Country	Name	City	State
Austria	Medical University of Graz	Graz
Austria	Salzburg Cancer Research Institute (SCRI)	Salzburg
Austria	Klinik Hietzing	Vienna
Belgium	ZNA Middelheim	Antwerp
Belgium	Institut Jules Bordet	Brussels
Belgium	Ghent University Hospital	Gent
Belgium	Hospital De Jolimont	La Louvière
Belgium	CHU de Liège	Liège
Belgium	AZ Delta	Roeselare
Belgium	CHU-UCL Namur	Yvoir
Canada	Tom Baker Cancer Centre	Calgary
Canada	Juravinski Cancer Centre	Hamilton	Ontario
Canada	London Health Sciences Center	London	Ontario
Canada	London Health Sciences Centre	London
Canada	McGill University Health Centre (MUHC)	Montréal	Quebec
Canada	Princess Margaret Cancer Centre - University Health Network	Toronto	Ontario
Canada	CancerCare Manitoba	Winnipeg	Manitoba
Czechia	Fakultni nemocnice Olomouc (University Hospital Olomouc)	Olomouc
Czechia	University Hospital Ostrava	Ostrava
Czechia	Nemocnice Pelhrimov	Pelhrimov
Czechia	General University Hospital Prague	Prague
France	CHU Amiens-Picardie	Amiens
France	CHU d'Angers	Angers
France	Centre Hospitalier de la Côte Basque Hématologie Clinique	Bayonne
France	Hôpital Avicenne	Bobigny
France	CHRU de BREST - Hôpital Morvan	Brest
France	CHU Clermont Ferrand / CHU Estaing	Clermont-Ferrand
France	CHU Grenoble Alpes Hôpital Nord Michallon	La Tronche
France	Hopital Mignot	Le Chesnay
France	CHU de Limoges	Limoges
France	Centre Léon Bérard	Lyon
France	CHU la Conception	Marseille
France	CHU Nantes - Hotel Dieu	Nantes
France	CHU de Nice - Hopital L'Archet	Nice
France	Hôpital Saint Louis	Paris
France	Centre Hospitalier de Perpignan	Perpignan
France	CHU Bordeaux	Pessac
France	CHU Lyon Sud	Pierre-Bénite
France	CHU Poiters	Poitiers
France	CHU Saint Etienne	Saint-Priest-en-Jarez
France	ICANS Strasbourg	Strasbourg
France	Institut Gustave Roussy	Villejuif
Germany	Universitätsklinikum Augsburg	Augsburg
Germany	Helios Klinikum Berlin Buch GmbH	Berlin
Germany	Universitätsklinikum Freiburg	Freiburg
Germany	Universitätsmedizin Göttingen	Göttingen
Germany	Universitätsklinikum Halle (Saale)	Halle
Germany	Universitätsklinikum Marburg	Marburg
Germany	Universitätsklinikum Münster	Münster
Hungary	Semmelweis Egyetem	Budapest
Hungary	Debrecen University Medical and Health Science Centre	Debrecen
Hungary	Markhot Ferenc Oktatókórház és Rendelointézet, Belgyógyászati- és Infektológiai Centrum	Eger
Hungary	Petz Aladar County Teaching Hospital	Gyor
Hungary	Josa Andras Teaching Hospital	Nyíregyháza
Israel	Barzilai Medical Center of Ashkelon	Ashkelon
Israel	Bnai Zion Medical center	Haifa
Israel	Carmel Medical Center	Haifa
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Sheba Medical Center	Ramat Gan
Israel	Kaplan Medical Center	Rehovot
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Italy	IRCCS Azienda Ospedaliero-Universitaria di Bologna	Bologna
Italy	ASST Spedali Civili di Brescia	Brescia
Italy	Azienda Ospedaliero-Universitaria di Ferrara	Ferrara
Italy	AOU Careggi	Firenze
Italy	Ospedale Policlinico San Martino	Genova
Italy	Romagnolo Institute to Study Tumors "Dino Amadori "/ Meldona	Meldola
Italy	A.O.U. Maggiore della Carità	Novara
Italy	Ospedali Marche Nord Centro Ematologia e Trapianti	Pesaro
Italy	Ospedale S.Maria delle Croci	Ravenna
Italy	Ospedale Infermi di Rimini	Rimini
Italy	Ospedale S. Eugenio - ASL Roma 2	Roma
Italy	Fondazione Policlinico Tor Vergata	Rome
Italy	AOUI di Verona	Verona
Poland	University Clinic Gdansk	Gdansk
Poland	Pomeranian Hospital Gdynia	Gdynia
Poland	Wojewodzki Szpital Specjalistyczny w Legnicy	Legnica
Poland	Alfred Sokolowski Hospital Walbrzych	Walbrzych
Poland	Instytut Hematologii i Transfuzjologii, Klinika Hematologii	Warszawa
Poland	University Clinic Warsaw	Warszawa
Spain	Institut Catala d'Oncologia - Hospital Duran i Reynals Location	Badalona
Spain	Fundación Privada Instituto de Investigación Oncológica Vall d'Hebron	Barcelona
Spain	H. Santa Creu i Sant Pau	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital del Mar Secretaria d'Hematologia Clínica	Barcelona
Spain	Hospital Universitario de Burgos	Burgos
Spain	Hospital San Pedro de Alcántara	Cáceres
Spain	H. Universitario La Paz	Madrid
Spain	Hospital Universitario de La Princesa	Madrid
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	MD Anderson Cancer Center	Madrid
Spain	Hospital General Universitario J.M. Morales Meseguer	Murcia
Spain	Hospital Universitario Central de Asturia	Oviedo
Spain	Hospital Son Llatzer	Palma De Mallorca
Spain	Clinica Universidad Navarra	Pamplona
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital Universitario Donostia	San Sebastián
Spain	Hospital Universitario Marqués de Valdecilla	Santander
Spain	Hospital Universitario Virgen Del Rocio	Seville
Spain	Hospital Clinico Universitario de Valencia	Valencia
Spain	Hospital Universitario y Politécnico La Fe	Valencia
United Kingdom	Castle Hill Hospital, Cottingham	Cottingham
United Kingdom	Ninewells Hospital	Dundee
United Kingdom	Western General Hospital in NHS Lothian Edinburgh Scotland	Edinburgh
United Kingdom	Clatterbridge Cancer Centre NHS Foundation Trust	Liverpool
United Kingdom	King's College Hospital NHS Foundation Trust	London
United Kingdom	The Royal Marsden Foundation Trust	London
United Kingdom	University Hospital Southampton NHS Foundation Trust	Southampton
United Kingdom	Sandwell and West Birmingham Hospital NHS Trust	West Bromwich
United States	Johns Hopkins University	Baltimore	Maryland
United States	American Oncology Partners of Maryland, PA	Bethesda	Maryland
United States	SCL Health Research Institute, Inc. (St. Vincent Frontier Cancer Center)	Billings	Montana
United States	Montefiore Medical Center & Albert Einstein College of Medicine	Bronx	New York
United States	Novant Health Inc	Charlotte	North Carolina
United States	University of Illinois Cancer Center	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	The Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	University of Iowa	Iowa City	Iowa
United States	UC Irvine	Irvine	California
United States	Cancer specialists of North Florida	Jacksonville	Florida
United States	Northwell Health	Lake Success	New York
United States	University of California, Los Angelas	Los Angeles	California
United States	University of Southern California	Los Angeles	California
United States	Morristown Medical Center- Atlantic Hematology Oncology	Morristown	New Jersey
United States	TriStar - Sarah Cannon BMT	Nashville	Tennessee
United States	Yale Cancer Center	New Haven	Connecticut
United States	Tulane Cancer Center	New Orleans	Louisiana
United States	Oregon Health and Science University	Portland	Oregon
United States	Comprehensive Hematology and Oncology	Saint Petersburg	Florida
United States	University of Utah Huntsman Cancer Institute	Salt Lake City	Utah
United States	Swedish Cancer Institute	Seattle	Washington
United States	Orchard Healthcare Research Inc.	Skokie	Illinois
United States	Moffitt Cancer Center	Tampa	Florida
United States	University of Arizona	Tucson	Arizona
United States	Novant Health Cancer Institute - Forsyth	Winston-Salem	North Carolina
United States	Wake Forest Baptist Health	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Syros Pharmaceuticals

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  Czechia,  France,  Germany,  Hungary,  Israel,  Italy,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Participants with Complete Remission		Up to 5 Years
Secondary	Duration of Overall Survival		Up to 5 Years
Secondary	Proportion of Participants Who Achieve Transfusion Independence		Up to 5 Years
Secondary	Proportion of Participants Who Achieve Objective Response		Up to 5 Years
Secondary	Duration of Complete Response		Up to 5 Years
Secondary	Duration of Overall Response		Up to 5 Years
Secondary	Time to Complete Remission		Up to 5 Years
Secondary	Time to Initial Response		Up to 5 Years
Secondary	Duration of Event Free Survival		Up to 5 Years
Secondary	Change in Health-Related Quality of Life (HRQOL) as assessed by the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 Scale (EORTC QLQ-30)		Up to 5 Years
Secondary	Change in HRQOL as assessed by the European Quality of Life 5 dimensions Scale (EuroQoL-5D)		Up to 5 Years
Secondary	Proportion of participants with Adverse Events and Serious Adverse Events		Up to 5 Years