Clinical trial NCT04797780: Tamibarotene 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 Tamibarotene Plus Azacitidine Versus Placebo Plus Azacitidine in Newly Diagnosed, Adult Patients Selected for RARA-positive Higher-risk Myelodysplastic Syndrome (SELECT MDS-1)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Myelodysplastic Syndromes
Keywords: Higher-Risk
Retinoic Acid Receptor Alpha (RARA) positive
Newly Diagnosed
Myelodysplastic Syndromes
Lead sponsor: Syros Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2021-03-15
Enrollment: 246
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 Tamibarotene plus azacitidine or placebo plus azacitidine.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With Complete Remission (CR)
timeFrame: Up to 45 months
Secondary outcomes:
measure: Duration of Overall Response (DOR)
timeFrame: Up to 45 months
measure: Number of Participants Who Achieved Transfusion Independence (TI)
timeFrame: Up to 45 months
measure: Percentage of Participants Who Achieved Overall Response (OR)
timeFrame: Up to 45 months
measure: Duration of Complete Response (DOCR)
timeFrame: Up to 45 months
measure: Time to Complete Remission (TCR)
timeFrame: Up to 45 months
measure: Time to Initial Response (TIR)
timeFrame: Up to 45 months
measure: 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)
timeFrame: Up to 45 months
measure: Change in HRQOL as Assessed by the European Quality of Life 5 Dimensions Scale (EuroQoL-5D)
timeFrame: Up to 45 months
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Up to 45 months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angelas
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Saint Petersburg
country: United States
facility: Comprehensive Hematology and Oncology
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Chicago
country: United States
facility: University of Illinois Cancer Center
state: Illinois
city: Skokie
country: United States
facility: Orchard Healthcare Research Inc.
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: New Orleans
country: United States
facility: Tulane Cancer Center
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Bethesda
country: United States
facility: American Oncology Partners of Maryland, PA
state: Maryland
city: Morristown
country: United States
facility: Morristown Medical Center- Atlantic Hematology Oncology
state: New Jersey
city: Lake Success
country: United States
facility: Northwell Health
state: New York
city: Charlotte
country: United States
facility: Novant Health Inc
state: North Carolina
city: Winston-Salem
country: United States
facility: Novant Health Cancer Institute - Forsyth
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University Comprehensive Cancer Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Nashville
country: United States
facility: TriStar - Sarah Cannon BMT
state: Tennessee
city: Salt Lake City
country: United States
facility: University of Utah Huntsman Cancer Institute
state: Utah
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Graz
country: Austria
facility: Medical University of Graz
city: Salzburg
country: Austria
facility: Salzburg Cancer Research Institute (SCRI)
city: Vienna
country: Austria
facility: Klinik Hietzing
city: Antwerp
country: Belgium
facility: ZNA Middelheim
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Gent
country: Belgium
facility: Ghent University Hospital
city: La Louvière
country: Belgium
facility: Hospital De Jolimont
city: Liège
country: Belgium
facility: CHU de Liège
city: Roeselare
country: Belgium
facility: AZ Delta
city: Yvoir
country: Belgium
facility: CHU-UCL Namur
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre
state: Ontario
city: London
country: Canada
facility: London Health Sciences Center
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre - University Health Network
state: Ontario
city: Montréal
country: Canada
facility: McGill University Health Centre (MUHC)
state: Quebec
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
city: London
country: Canada
facility: London Health Sciences Centre
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc (University Hospital Olomouc)
city: Ostrava
country: Czechia
facility: University Hospital Ostrava
city: Prague
country: Czechia
facility: General University Hospital Prague
city: Amiens
country: France
facility: CHU Amiens-Picardie
city: Angers
country: France
facility: CHU d'Angers
city: Bayonne
country: France
facility: Centre Hospitalier de la Côte Basque Hématologie Clinique
city: Bobigny
country: France
facility: Hôpital Avicenne
city: Brest
country: France
facility: CHRU de BREST - Hôpital Morvan
city: Clermont-Ferrand
country: France
facility: CHU Clermont Ferrand / CHU Estaing
city: La Tronche
country: France
facility: CHU Grenoble Alpes Hôpital Nord Michallon
city: Le Chesnay
country: France
facility: Hopital Mignot
city: Limoges
country: France
facility: CHU de Limoges
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: CHU la Conception
city: Nantes
country: France
facility: CHU Nantes - Hotel Dieu
city: Nice
country: France
facility: CHU de Nice - Hopital L'Archet
city: Paris
country: France
facility: Hôpital Saint Louis
city: Pessac
country: France
facility: CHU Bordeaux
city: Pierre-Bénite
country: France
facility: CHU Lyon Sud
city: Poitiers
country: France
facility: CHU Poiters
city: Saint-Priest-en-Jarez
country: France
facility: CHU Saint Etienne
city: Strasbourg
country: France
facility: ICANS Strasbourg
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Augsburg
country: Germany
facility: Universitätsklinikum Augsburg
city: Berlin
country: Germany
facility: Helios Klinikum Berlin Buch GmbH
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg
city: Göttingen
country: Germany
facility: Universitätsmedizin Göttingen
city: Halle
country: Germany
facility: Universitätsklinikum Halle (Saale)
city: Marburg
country: Germany
facility: Universitätsklinikum Marburg
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Debrecen
country: Hungary
facility: Debrecen University Medical and Health Science Centre
city: Eger
country: Hungary
facility: Markhot Ferenc Oktatókórház és Rendelőintézet, Belgyógyászati- és Infektológiai Centrum
city: Győr
country: Hungary
facility: Petz Aladar County Teaching Hospital
city: Nyíregyháza
country: Hungary
facility: Josa Andras Teaching Hospital
city: Ashkelon
country: Israel
facility: Barzilai Medical Center of Ashkelon
city: Haifa
country: Israel
facility: Bnai Zion Medical center
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Rehovot
country: Israel
facility: Kaplan Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Bologna
country: Italy
facility: IRCCS Azienda Ospedaliero-Universitaria di Bologna
city: Brescia
country: Italy
facility: ASST Spedali Civili di Brescia
city: Ferrara
country: Italy
facility: Azienda Ospedaliero-Universitaria di Ferrara
city: Firenze
country: Italy
facility: AOU Careggi
city: Genova
country: Italy
facility: Ospedale Policlinico San Martino
city: Meldola
country: Italy
facility: Romagnolo Institute to Study Tumors "Dino Amadori "/ Meldona
city: Novara
country: Italy
facility: A.O.U. Maggiore della Carità
city: Pesaro
country: Italy
facility: Ospedali Marche Nord Centro Ematologia e Trapianti
city: Ravenna
country: Italy
facility: Ospedale S.Maria delle Croci
city: Roma
country: Italy
facility: Ospedale S. Eugenio - ASL Roma 2
city: Rome
country: Italy
facility: Fondazione Policlinico Tor Vergata
city: Verona
country: Italy
facility: AOUI di Verona
city: Gdańsk
country: Poland
facility: University Clinic Gdansk
city: Gdynia
country: Poland
facility: Pomeranian Hospital Gdynia
city: Legnica
country: Poland
facility: Wojewodzki Szpital Specjalistyczny w Legnicy
city: Warszawa
country: Poland
facility: Instytut Hematologii i Transfuzjologii, Klinika Hematologii
city: Warszawa
country: Poland
facility: University Clinic Warsaw
city: Wałbrzych
country: Poland
facility: Alfred Sokołowski Hospital Wałbrzych
city: Badalona
country: Spain
facility: Institut Catala d'Oncologia - Hospital Duran i Reynals Location
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: H. Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Fundación Privada Instituto de Investigación Oncológica Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital del Mar Secretaria d'Hematologia Clínica
city: Burgos
country: Spain
facility: Hospital Universitario de Burgos
city: Cáceres
country: Spain
facility: Hospital San Pedro de Alcántara
city: Madrid
country: Spain
facility: MD Anderson Cancer Center
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: H. Universitario La Paz
city: Madrid
country: Spain
facility: Hospital Universitario de La Princesa
city: Murcia
country: Spain
facility: Hospital General Universitario J.M. Morales Meseguer
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturia
city: Palma De Mallorca
country: Spain
facility: Hospital Son Llatzer
city: Pamplona
country: Spain
facility: Clinica Universidad Navarra
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: San Sebastián
country: Spain
facility: Hospital Universitario Donostia
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
city: Seville
country: Spain
facility: Hospital Universitario Virgen Del Rocio
city: Valencia
country: Spain
facility: Hospital Universitario y Politécnico La Fe
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Cottingham
country: United Kingdom
facility: Castle Hill Hospital, Cottingham
city: Dundee
country: United Kingdom
facility: Ninewells Hospital
city: Edinburgh
country: United Kingdom
facility: Western General Hospital in NHS Lothian Edinburgh Scotland
city: Liverpool
country: United Kingdom
facility: Clatterbridge Cancer Centre NHS Foundation Trust
city: London
country: United Kingdom
facility: King's College Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: The Royal Marsden Foundation Trust
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust
city: West Bromwich
country: United Kingdom
facility: Sandwell and West Birmingham Hospital NHS Trust
Study officials:
affiliation: Syros Pharmaceuticals Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: