Guadecitabine (SGI-110) vs Treatment Choice in Adults With MDS or CMML Previously Treated With HMAs

Last updated: July 31, 2024
Sponsor: Astex Pharmaceuticals, Inc.
Overall Status: Completed

Phase

3

Condition

Leukemia

Myelodysplastic Syndromes (Mds)

White Cell Disorders

Treatment

Guadecitabine

Treatment Choice

Clinical Study ID

NCT02907359
SGI-110-07
2015-005257-12
  • Ages > 18
  • All Genders

Study Summary

A Phase 3, randomized, open-label, parallel-group, multicenter study designed to evaluate the efficacy and safety of guadecitabine in participants with MDS or CMML who failed or relapsed after adequate prior treatment with azacitidine, decitabine, or both. This global study will be conducted in approximately 15 countries. Approximately 408 participants from approximately 100 study centers will be randomly assigned in a 2:1 ratio to either guadecitabine (approximately 272 participants) or Treatment Choice (approximately 136 participants). The study consists of a 21-day screening period, a treatment period, a safety follow-up visit, and a long-term follow-up period. The study is expected to last more than 2 years, and the duration of individual participant participation will vary. Participants may continue to receive treatment for as long as they continue to benefit.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Adult participants ≥18 years of age who are able to understand and comply with studyprocedures and provide written informed consent before any study-specific procedure.

  • Cytologically or histologically confirmed diagnosis of MDS or CMML according to the 2008 World Health Organization (WHO) classification.

  • Performance status (ECOG) of 0-2.

  • Previously treated MDS or CMML, defined as prior treatment with at least onehypomethylating agent (HMA; azacitidine and/or decitabine) for intermediate or highrisk MDS or CMML whose disease progressed or relapsed as follows:

  1. Participant received HMA for at least 6 cycles and was still transfusiondependent.

  2. Participant received HMA for at least 2 complete cycles and had diseaseprogression prior to Cycle 6 defined as i. ≥50% increase in bone marrow blasts from pre-HMA-treatment levels or from nadirpost-HMA-treatment levels to >5% (for participants with pretreatment or nadir blasts ≤5%) or to >10% (for participants with pretreatment or nadir blasts >5%), and/or ii.Transfusion dependent and ≥2 gram/deciliter (g/dL) reduction of Hgb frompre-HMA-treatment levels.

Other prior treatments for MDS such as lenalidomide, cytarabine, intensive chemotherapy, hydroxyurea, erythropoietin and other growth factors, or hematopoietic cell transplant (HCT) are allowed.

  • Participants must have either:

  1. Bone marrow blasts >5% at randomization, OR

  2. Transfusion dependence, defined as having had transfusion (in the setting ofactive disease) of 2 or more units of RBC or platelets within 8 weeks prior torandomization.

  • Creatinine clearance or glomerular filtration rate ≥30 milliliter/minute (mL/min)estimated by the Cockroft-Gault (C-G) or other medically acceptable formulas such asMDRD (Modification of Diet in Renal Disease) or CKD-EPI (the Chronic Kidney DiseaseEpidemiology Collaboration).

  • Women of childbearing potential must not be pregnant or breastfeeding and must havea negative pregnancy test at screening. Women of childbearing potential and men withfemale partners of childbearing potential must agree to practice 2 highly effectivecontraceptive measures of birth control and must agree not to become pregnant orfather a child (a) while receiving treatment with guadecitabine and for at least 3months after completing treatment and (b) while receiving treatment with LDAC or ICand for at least 6 months after completing treatment or for the duration specifiedin local prescribing information, whichever is longer.

Exclusion

Exclusion Criteria:

  • Participants who have been diagnosed as having AML with peripheral blood or bonemarrow blasts of ≥20%.

  • Participants who may still be sensitive to repeated treatment with decitabine orazacitidine such as participants who had response to prior decitabine or azacitidinetreatment, but relapsed >6 months after stopping treatment with these agents.

  • Prior treatment with guadecitabine.

  • Hypersensitivity to decitabine, guadecitabine, or any of their excipients.

  • Second malignancy currently requiring active therapy, except breast or prostatecancer stable on or responding to endocrine therapy.

  • Treated with any investigational drug within 2 weeks of the first dose of studytreatment.

  • Total serum bilirubin >2.5 × upper limit of normal (ULN) (except for participantswith Gilbert's Syndrome for whom direct bilirubin is <2.5×ULN), or liver cirrhosisor chronic liver disease Child-Pugh Class B or C.

  • Known active HIV, HBV, or HCV infection. Inactive hepatitis carrier status or lowviral hepatitis titer on antivirals is allowed.

  • Known significant mental illness or other condition such as active alcohol or othersubstance abuse or addiction that, in the opinion of the investigator, predisposesthe participant to high risk of noncompliance with the protocol.

  • Refractory congestive heart failure unresponsive to medical treatment, activeinfection resistant to all antibiotics, or advanced non-MDS associated pulmonarydisease requiring >2 liters per minute oxygen.

  • Life expectancy of less than one month

  • Participants with TP53 mutations

Study Design

Total Participants: 417
Treatment Group(s): 2
Primary Treatment: Guadecitabine
Phase: 3
Study Start date:
January 13, 2017
Estimated Completion Date:
November 30, 2020

Study Description

Multicenter, randomized, open-label, parallel-group study of guadecitabine vs Treatment Choice (TC). Approximately 408 participants will be randomly assigned 2:1 to either guadecitabine or TC.

  • Guadecitabine: approximately 272 participants.

  • TC: approximately 136 participants.

Before randomization, the investigator will assign each participant to one of the following TC options:

  • Low dose cytarabine (LDAC).

  • Standard Intensive Chemotherapy (IC) of a 7+3 regimen.

  • Best Supportive Care (BSC) only. BSC will be provided to all participants as per standard and institutional practice. Participants randomized to TC will not be allowed to cross over to guadecitabine. Data will be reviewed by an independent Data Monitoring Committee at regular intervals, primarily to evaluate safety during study conduct. Randomization will be stratified by disease category (MDS vs CMML), bone marrow (BM) blasts (BM blasts >10% vs BM blasts ≤10%), TC option (LDAC vs IC vs BSC), and study center region.

Guadecitabine: 60 milligrams per square meter (mg/m^2) given subcutaneously (SC) daily on Days 1-5 in 28-day cycles (delayed as needed to allow blood count recovery). Treatment should be given for at least 6 total cycles in the absence of unacceptable toxicity or disease progression requiring alternative therapy. Beyond 6 cycles, treatment should continue as long as the participant continues to benefit. BSC should be given according to standard and institutional practice.

Treatment Choice (TC): Before randomization, the investigator will assign each participant to one of the following TC options:

  • Low dose cytarabine (LDAC) given as 20 mg/m^2 SC or intravenously (IV) once daily for 14 days in 28-day cycles (delayed as needed to allow blood count recovery). Treatment should be given for at least 4 cycles in the absence of disease progression or unacceptable toxicity.

  • Standard Intensive Chemotherapy (IC) of a 7+3 regimen: given as cytarabine 100-200 mg/m^2/day given as continuous infusion for 7 days and an anthracycline given as per institutional standard practice such as daunorubicin (45-60 mg/m^2/day), or idarubicin (9-12 mg/m^2/day), or mitoxantrone (8-12 mg/m^2/day) by intravenous infusion for 3 days.

  • Best Supportive Care (BSC) only: given according to standard and institutional practice. BSC includes, but is not limited to blood transfusions (Red blood cells [RBCs] or platelets), growth factors including erythropoiesis stimulating agents (ESA), granulocyte stimulating factors (GSFs), iron chelating therapy, and broad-spectrum antibiotics and/or antifungals.

Connect with a study center

  • Ziekenhuis Netwerk Antwerpen Stuivenberg

    Antwerp,
    Belgium

    Site Not Available

  • Algemeen Ziekenhuis Sint-Jan Brugge-Oostende

    Brugge,
    Belgium

    Site Not Available

  • Grand Hôpital de Charleroi - Notre Dame

    Charleroi,
    Belgium

    Site Not Available

  • Tom Baker Cancer Center

    Calgary, Alberta T2N 4N2
    Canada

    Site Not Available

  • University of Alberta Hospital

    Edmonton, Alberta T6G 2B7
    Canada

    Site Not Available

  • Royal Victoria Regional Health Centre

    Barrie, Ontario L4M 6M2
    Canada

    Site Not Available

  • Juravinski Cancer Centre

    Hamilton, Ontario L8V 1C3
    Canada

    Site Not Available

  • Princess Margaret Hospital

    Toronto, Ontario M5G 2C1
    Canada

    Site Not Available

  • Burnaby Hospital

    Burnaby,
    Canada

    Site Not Available

  • Moncton Hospital

    Moncton,
    Canada

    Site Not Available

  • Maisonneuve-Rosemont Hôpital Service d'Hematologie et d'Oncologie Medicale

    Montréal,
    Canada

    Site Not Available

  • Saskatchewan Cancer Agency

    Regina,
    Canada

    Site Not Available

  • Fakultní nemocnice Brno

    Brno,
    Czechia

    Site Not Available

  • Fakultni Nemocnice Hradec Králové

    Hradec Králové,
    Czechia

    Site Not Available

  • Fakultní nemocnice Ostrava

    Ostrava,
    Czechia

    Site Not Available

  • Fakultní Nemocnice Královské Vinohrady

    Praha,
    Czechia

    Site Not Available

  • Onkologická klinika Všeobecná fakultní nemocnice v Praze a 1

    Praha 2,
    Czechia

    Site Not Available

  • Aalborg Universitetshospital

    Aalborg,
    Denmark

    Site Not Available

  • Aarhus Universitetshospital

    Aarhus,
    Denmark

    Site Not Available

  • Rigshospitalet

    Copenhagen,
    Denmark

    Site Not Available

  • Odense University Hospital

    Odense,
    Denmark

    Site Not Available

  • Centre Hospitalier Universitaire

    La Tronche,
    France

    Site Not Available

  • Hôpital Dupuytren

    Limoges,
    France

    Site Not Available

  • GHR Mulhouse Sud-Alsace

    Mulhouse Cedex,
    France

    Site Not Available

  • Hôpital Hôtel-Dieu

    Nantes,
    France

    Site Not Available

  • Centre Antoine Lacassagne

    Nice,
    France

    Site Not Available

  • Hôpital Saint Louis

    Paris,
    France

    Site Not Available

  • Centre Hospitalier Lyon Sud

    Pierre-Bénite,
    France

    Site Not Available

  • Centre Hospitalier Universitaire de Toulouse

    Toulouse,
    France

    Site Not Available

  • Städtisches Klinikum Braunschweig

    Braunschweig,
    Germany

    Site Not Available

  • Marien Hospital Düsseldorf

    Düsseldorf,
    Germany

    Site Not Available

  • Universitaetsklinikum Freiburg

    Freiburg,
    Germany

    Site Not Available

  • Universitätsklinikum Halle

    Halle,
    Germany

    Site Not Available

  • Universitätsklinikum Ulm

    Ulm,
    Germany

    Site Not Available

  • Azienda Ospedaliera SS. Antonio E. Biagio E. Cesare Arrigo di Alessandria

    Alessandria,
    Italy

    Site Not Available

  • Azienda Ospedaliero Universitaria Careggi

    Firenze,
    Italy

    Site Not Available

  • Azienda Ospedaliera Universitaria San Martino

    Genova,
    Italy

    Site Not Available

  • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

    Milano,
    Italy

    Site Not Available

  • AORN A. Cardarelli

    Napoli,
    Italy

    Site Not Available

  • Azienda Ospedaliera Universitaria-Maggiore della Carità di Novara

    Novara,
    Italy

    Site Not Available

  • Azienda Ospedaliera Ospedali Riuniti Marche Nord

    Pesaro,
    Italy

    Site Not Available

  • Ospedale S. Eugenio

    Roma,
    Italy

    Site Not Available

  • NHO Nagoya Medical Center

    Nagoya-shi, Aichi
    Japan

    Site Not Available

  • Narita Red Cross Hospital

    Narita, Chiba
    Japan

    Site Not Available

  • University of Fukui Hospital

    Yoshida, Fukui
    Japan

    Site Not Available

  • Chugoku Central Hospital

    Fukuyama-shi, Hiroshima
    Japan

    Site Not Available

  • Tokai University Hospital

    Isehara, Kanagawa
    Japan

    Site Not Available

  • Kitasato University Hospital

    Sagamihara-shi, Kanagawa
    Japan

    Site Not Available

  • Yokohama Municipal Citizen's Hospital

    Yokohama, Kanagawa
    Japan

    Site Not Available

  • Nagasaki University Hospital

    Nagasaki, Nagasaki-shi
    Japan

    Site Not Available

  • Kansai Medical University Hirakata

    Hirakata, Osaka
    Japan

    Site Not Available

  • Kindai University Hospital

    Osakasayama-shi, Osaka
    Japan

    Site Not Available

  • Saitama Medical Center

    Kawagoe, Saitama
    Japan

    Site Not Available

  • Nippon Medical School Hospital

    Bunkyō-Ku, Tokyo
    Japan

    Site Not Available

  • The Cancer Institute Hospital of Japanese Foundation for Cancer Research

    Koto, Tokyo
    Japan

    Site Not Available

  • NTT Medical Center Tokyo

    Shinagawa, Tokyo
    Japan

    Site Not Available

  • National Hospital Organization Disaster Medical Center

    Tachikawa, Tokyo
    Japan

    Site Not Available

  • empty

    Chubu,
    Japan

    Site Not Available

  • Chubu,
    Japan

    Site Not Available

  • empty

    Chugoku,
    Japan

    Site Not Available

  • Chugoku,
    Japan

    Site Not Available

  • National Hospital Organization Kyushu

    Fukuoka,
    Japan

    Site Not Available

  • Fukushima Medical University

    Fukushima,
    Japan

    Site Not Available

  • Gifu Municipal Hospital

    Gifu,
    Japan

    Site Not Available

  • empty

    Kanto,
    Japan

    Site Not Available

  • Kanto,
    Japan

    Site Not Available

  • empty

    Kinki,
    Japan

    Site Not Available

  • Kinki,
    Japan

    Site Not Available

  • National Hospital Organization Kumamoto Medical Center

    Kumamoto,
    Japan

    Site Not Available

  • Japanese Red Cross Kyoto Daini Hospital

    Kyoto,
    Japan

    Site Not Available

  • University Hospital-Kyoto Prefectural University of Medicine

    Kyoto,
    Japan

    Site Not Available

  • empty

    Kyushu,
    Japan

    Site Not Available

  • Kyushu,
    Japan

    Site Not Available

  • empty

    Tohoku,
    Japan

    Site Not Available

  • Tohoku,
    Japan

    Site Not Available

  • Yamagata University Hospital

    Yamagata,
    Japan

    Site Not Available

  • Asan Medical Center

    Seoul, 05505
    Korea, Republic of

    Site Not Available

  • Samsung Medical Center

    Seoul, 06351
    Korea, Republic of

    Site Not Available

  • Seoul National University Hospital

    Seoul, 03080
    Korea, Republic of

    Site Not Available

  • Seoul Saint Mary's Hospital

    Seoul, 137-701
    Korea, Republic of

    Site Not Available

  • Severance Hospital, Yonsei University Health System

    Seoul, 03722
    Korea, Republic of

    Site Not Available

  • Ulsan University Hospital

    Ulsan, 44033
    Korea, Republic of

    Site Not Available

  • Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie

    Lublin,
    Poland

    Site Not Available

  • Instytut Hematologii i Transfuzjologii

    Warszawa,
    Poland

    Site Not Available

  • Samodzielny Publiczny Centralny Szpital Kliniczny

    Warszawa,
    Poland

    Site Not Available

  • Hospital General Universitario de Alicante

    Alicante,
    Spain

    Site Not Available

  • Hospital Universitari Germans Trias i Pujol

    Badalona,
    Spain

    Site Not Available

  • Fundació Hospital de la Santa Creu i Sant Pau

    Barcelona,
    Spain

    Site Not Available

  • Hospital Universitario Vall d'Hebron

    Barcelona,
    Spain

    Site Not Available

  • Hospital San Pedro de Alcantara

    Cáceres,
    Spain

    Site Not Available

  • Hospital de León

    León,
    Spain

    Site Not Available

  • Hospital General Universitario Gregorio Marañon

    Madrid,
    Spain

    Site Not Available

  • Hospital Universitario 12 de Octubre

    Madrid,
    Spain

    Site Not Available

  • Hospital Universitario Ramón Y Cajal

    Madrid,
    Spain

    Site Not Available

  • Hospital Universitario de Salamanca

    Salamanca,
    Spain

    Site Not Available

  • Hospital Universitari i Politecnic La Fe de Valencia

    Valencia,
    Spain

    Site Not Available

  • Sahlgrenska Universitetssjukhuset, Östra sjukhuset

    Göteborg,
    Sweden

    Site Not Available

  • Universitetssjukhuset Örebro

    Örebro,
    Sweden

    Site Not Available

  • Medway NHS Foundation Trust

    Gillingham,
    United Kingdom

    Site Not Available

  • The Leeds Teaching Hospitals NHS Trust

    Leeds,
    United Kingdom

    Site Not Available

  • Chelsea and Westminster Hospital NHS Foundation Trust

    London,
    United Kingdom

    Site Not Available

  • Nottingham University Hospitals NHS Trust

    Nottingham,
    United Kingdom

    Site Not Available

  • City of Hope

    Duarte, California 91010
    United States

    Site Not Available

  • Desert Hematology Oncology Medical Group, Inc.

    Rancho Mirage, California 92270
    United States

    Site Not Available

  • Cancer Specialists of North Florida

    Fleming Island, Florida 32003
    United States

    Site Not Available

  • Mount Sinai Medical Center

    Miami Beach, Florida 33140
    United States

    Site Not Available

  • Rush University Medical Center

    Chicago, Illinois 60612
    United States

    Site Not Available

  • North Shore Medical Center

    Evanston, Illinois 60201
    United States

    Site Not Available

  • Franciscan Health Indianapolis

    Indianapolis, Indiana 46237
    United States

    Site Not Available

  • University of Maryland

    Baltimore, Maryland 21201
    United States

    Site Not Available

  • University of Michigan Cancer Center

    Ann Arbor, Michigan 48109
    United States

    Site Not Available

  • John Theurer Cancer Center

    Hackensack, New Jersey 07601
    United States

    Site Not Available

  • Roswell Park Cancer Institute

    Buffalo, New York 14263
    United States

    Site Not Available

  • Weill Cornell Medical College

    New York, New York 10065
    United States

    Site Not Available

  • Stony Brook University Medical Center

    Stony Brook, New York 11794
    United States

    Site Not Available

  • Duke Cancer Center

    Durham, North Carolina 27705
    United States

    Site Not Available

  • Penn State Milton S. Hershey Medical Center

    Hershey, Pennsylvania 17033
    United States

    Site Not Available

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania 19111
    United States

    Site Not Available

  • Medical University of South Carolina

    Charleston, South Carolina 29425
    United States

    Site Not Available

  • Bon Secours Saint Francis Hospital

    Greenville, South Carolina 29607
    United States

    Site Not Available

  • University of Texas MD Anderson Cancer Center

    Houston, Texas 77030
    United States

    Site Not Available

  • Fred Hutchinson Cancer Research Center

    Seattle, Washington 98109
    United States

    Site Not Available

  • Swedish Cancer Institute

    Seattle, Washington 98104
    United States

    Site Not Available

  • West Virginia University Mary Babb Randolph Cancer Center

    Morgantown, West Virginia 26506
    United States

    Site Not Available

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.