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

Astex Pharmaceuticals, Inc. (Industry)
Overall Status
Completed ID

Study Details

Study Description

Brief Summary

A Phase 3, randomized, open-label, parallel-group, multicenter study designed to evaluate the efficacy and safety of guadecitabine in subjects 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 subjects from approximately 100 study centers will be randomly assigned in a 2:1 ratio to either guadecitabine (approximately 272 subjects) or Treatment Choice (approximately 136 subjects). The study consists of a 14-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 subject participation will vary. Subjects may continue to receive treatment for as long as they continue to benefit.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

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

  • Guadecitabine: approximately 272 subjects.

  • TC: approximately 136 subjects.

Before randomization, the investigator will assign each subject 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 subjects as per standard and institutional practice. Subjects 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 mg/m2 given 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 subject continues to benefit. BSC should be given according to standard and institutional practice.

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

  • Low dose cytarabine (LDAC) given as 20 mg/m2 SC or 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/m2/day given as continuous infusion for 7 days and an anthracycline given as per institutional standard practice such as daunorubicin (45-60 mg/m2/day), or idarubicin (9-12 mg/m2/day), or mitoxantrone (8-12 mg/m2/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 (RBCs or platelets), growth factors including erythropoiesis stimulating agents (ESA), granulocyte stimulating factors (GSFs), iron chelating therapy, and broad spectrum antibiotics and/or antifungals.

Study Design

Study Type:
Actual Enrollment :
408 participants
Intervention Model:
Parallel Assignment
None (Open Label)
Primary Purpose:
Official Title:
A Phase 3, Multicenter, Randomized, Open-Label Study of Guadecitabine (SGI-110) Versus Treatment Choice in Adults With Myelodysplastic Syndromes (MDS) or Chronic Myelomonocytic Leukemia (CMML) Previously Treated With Hypomethylating Agents
Actual Study Start Date :
Oct 1, 2016
Actual Primary Completion Date :
Mar 31, 2020
Actual Study Completion Date :
Nov 30, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Guadecitabine

Guadecitabine 60 mg/m2 given subcutaneously daily on Days 1-5 in 28-day cycles. The total amount (in mg) of guadecitabine to be administered is determined by body surface area.

Drug: Guadecitabine
Guadecitabine regimen is 60 mg/m2 given 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 absence of unacceptable toxicity or disease progression requiring alternative therapy.
Other Names:
  • SGI-110
  • Active Comparator: Treatment Choice

    Best Supportive Care. Low dose cytarabine. Standard Intensive Chemotherapy.

    Other: Treatment Choice
    BSC: according to standard/institutional practice; includes RBC or platelet transfusions; growth factors, ie, erythropoiesis stimulating agents, granulocyte stimulating factors, iron chelating therapy; broad spectrum antibiotics and/or antifungals. Low dose cytarabine: 20 mg/m2 SC or IV QD for 14 days in 28-day cycles. Other schedules allowed per institutional practice. Treatment for ≥4 cycles absent disease progression/toxicity. BSC per institutional/standard practice. Standard Intensive Chemotherapy: recommended 7+3 given as cytarabine 100-200 mg/m2/day continuous infusion for 7 days and an anthracycline for 3 days. Anthracyclines per institutional practice include daunorubicin (45-60 mg/m2/day) or idarubicin (9-12 mg/m2/day) or mitoxantrone (8-12 mg/m2/day) by IV infusion. Subjects with complete or partial response after IC induction should receive ≥1 additional cycles with reduced cytotoxic doses then BSC per standard /institutional practice.

    Outcome Measures

    Primary Outcome Measures

    1. Overall survival [18 Months]

    Secondary Outcome Measures

    1. Transfusion independence [18 months]

    2. Marrow complete response [18 months]

    3. Survival rate [18 months]

    4. Leukemia-free survival [18 months]

      As described in Time Frame.

    5. Number of days alive and out of the hospital (NDAOH). [18 months]

    6. Disease response [18 months]

    7. Duration of response [18 months]

    8. Number of transfusions [18 months]

    9. Health-related quality of life [18 months]

    10. Incidence and severity of adverse events. [18 months]

    11. 30-day and 60-day all-cause mortality [18 months]

    Eligibility Criteria


    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Accepts Healthy Volunteers:
    Inclusion Criteria:
    • Adult subjects ≥18 years of age who are able to understand and comply with study procedures, 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 one hypomethylating agent (HMA; azacitidine and/or decitabine) for intermediate or high risk MDS or CMML whose disease progressed or relapsed as follows:

    1. Subject received HMA for at least 6 cycles and was still transfusion dependent (as defined in 5b below).

    2. Subject had disease progression prior to Cycle 6 defined as ≥50% increase in bone marrow blasts from pretreatment levels to >5%, or ≥2 g/dL reduction of Hgb from pretreatment levels with transfusion dependence after at least 2 cycles of HMA.

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

    • Subjects must have either:
    1. Bone marrow blasts >5% at randomization, OR

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

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

    • Women of childbearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. Women of childbearing potential and men with female partners of childbearing potential must agree to practice 2 highly effective contraceptive measures of birth control and must agree not to become pregnant or father a child while receiving treatment with guadecitabine, LDAC, or IC and for at least 3 months after completing treatment.

    Exclusion criteria:
    • Subjects who have been diagnosed as having AML with peripheral blood or bone marrow blasts of ≥20%.

    • Subjects who may still be sensitive to repeated treatment with decitabine or azacitidine such as subjects who had response to prior decitabine or azacitidine treatment, 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 prostate cancer stable on or responding to endocrine therapy.

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

    • Total serum bilirubin >2.5 ULN (except for subjects with Gilbert's Syndrome for whom direct bilirubin is <2.5×ULN), or liver cirrhosis or chronic liver disease Child-Pugh Class B or C.

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

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

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

    • Life expectancy of less than one month

    • subjects with TP53 mutations

    Contacts and Locations


    Site City State Country Postal Code
    1 City of Hope Duarte California United States 91010
    2 Desert Hematology Oncology Medical Group, Inc. Rancho Mirage California United States 92270
    3 Cancer Specialists of North Florida Fleming Island Florida United States 32003
    4 Mount Sinai Medical Center Miami Beach Florida United States 33140
    5 Rush University Medical Center Chicago Illinois United States 60612
    6 North Shore Medical Center Evanston Illinois United States 60201
    7 Franciscan Health Indianapolis Indianapolis Indiana United States 46237
    8 University of Maryland Baltimore Maryland United States 21201
    9 University of Michigan Cancer Center Ann Arbor Michigan United States 48109
    10 John Theurer Cancer Center Hackensack New Jersey United States 07601
    11 Roswell Park Cancer Institute Buffalo New York United States 14263
    12 Weill Cornell Medical College New York New York United States 10065
    13 Stony Brook University Medical Center Stony Brook New York United States 11794
    14 Duke Cancer Center Durham North Carolina United States 27705
    15 Penn State Milton S. Hershey Medical Center Hershey Pennsylvania United States 17033
    16 Fox Chase Cancer Center Philadelphia Pennsylvania United States 19111
    17 Medical University of South Carolina Charleston South Carolina United States 29425
    18 Bon Secours Saint Francis Hospital Greenville South Carolina United States 29607
    19 University of Texas MD Anderson Cancer Center Houston Texas United States 77030
    20 Swedish Cancer Institute Seattle Washington United States 98104
    21 Fred Hutchinson Cancer Research Center Seattle Washington United States 98109
    22 West Virginia University Mary Babb Randolph Cancer Center Morgantown West Virginia United States 26506
    23 Ziekenhuis Netwerk Antwerpen Stuivenberg Antwerp Belgium
    24 Algemeen Ziekenhuis Sint-Jan Brugge-Oostende Brugge Belgium
    25 Grand Hôpital de Charleroi - Notre Dame Charleroi Belgium
    26 Tom Baker Cancer Center Calgary Alberta Canada T2N 4N2
    27 University of Alberta Hospital Edmonton Alberta Canada T6G 2B7
    28 Royal Victoria Regional Health Centre Barrie Ontario Canada L4M 6M2
    29 Juravinski Cancer Centre Hamilton Ontario Canada L8V 1C3
    30 Princess Margaret Hospital Toronto Ontario Canada M5G 2C1
    31 Burnaby Hospital Burnaby Canada
    32 Moncton Hospital Moncton Canada
    33 Maisonneuve-Rosemont Hôpital Service d'Hematologie et d'Oncologie Medicale Montréal Canada
    34 Saskatchewan Cancer Agency Regina Canada
    35 Fakultní nemocnice Brno Brno Czechia
    36 Fakultni Nemocnice Hradec Králové Hradec Králové Czechia
    37 Fakultní nemocnice Ostrava Ostrava Czechia
    38 Onkologická klinika Všeobecná fakultní nemocnice v Praze a 1 Praha 2 Czechia
    39 Fakultní Nemocnice Královské Vinohrady Praha Czechia
    40 Aalborg Universitetshospital Aalborg Denmark
    41 Aarhus Universitetshospital Aarhus Denmark
    42 Rigshospitalet Copenhagen Denmark
    43 Odense University Hospital Odense Denmark
    44 Centre Hospitalier Universitaire La Tronche France
    45 Hôpital Dupuytren Limoges France
    46 GHR Mulhouse Sud-Alsace Mulhouse Cedex France
    47 Hôpital Hôtel-Dieu Nantes France
    48 Centre Antoine Lacassagne Nice France
    49 Hôpital Saint Louis Paris France
    50 Centre Hospitalier Lyon Sud Pierre-Bénite France
    51 Centre Hospitalier Universitaire de Toulouse Toulouse France
    52 Städtisches Klinikum Braunschweig Braunschweig Germany
    53 Marien Hospital Düsseldorf Düsseldorf Germany
    54 Universitaetsklinikum Freiburg Freiburg Germany
    55 Universitätsklinikum Halle Halle Germany
    56 Universitätsklinikum Ulm Ulm Germany
    57 Azienda Ospedaliera SS. Antonio E. Biagio E. Cesare Arrigo di Alessandria Alessandria Italy
    58 Azienda Ospedaliero Universitaria Careggi Firenze Italy
    59 Azienda Ospedaliera Universitaria San Martino Genova Italy
    60 Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano Italy
    61 AORN A. Cardarelli Napoli Italy
    62 Azienda Ospedaliera Universitaria-Maggiore della Carità di Novara Novara Italy
    63 Azienda Ospedaliera Ospedali Riuniti Marche Nord Pesaro Italy
    64 Ospedale S. Eugenio Roma Italy
    65 Chubu Japan
    66 Chugoku Japan
    67 Kanto Japan
    68 Kinki Japan
    69 Kyushu Japan
    70 Tohoku Japan
    71 Seoul National University Hospital Seoul Korea, Republic of 03080
    72 Severance Hospital, Yonsei University Health System Seoul Korea, Republic of 03722
    73 Asan Medical Center Seoul Korea, Republic of 05505
    74 Samsung Medical Center Seoul Korea, Republic of 06351
    75 Seoul Saint Mary's Hospital Seoul Korea, Republic of 137-701
    76 Ulsan University Hospital Ulsan Korea, Republic of 44033
    77 Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie Lublin Poland
    78 Instytut Hematologii i Transfuzjologii Warszawa Poland
    79 Samodzielny Publiczny Centralny Szpital Kliniczny Warszawa Poland
    80 Hospital General Universitario de Alicante Alicante Spain
    81 Hospital Universitari Germans Trias i Pujol Badalona Spain
    82 Fundació Hospital de la Santa Creu i Sant Pau Barcelona Spain
    83 Hospital Universitario Vall d'Hebron Barcelona Spain
    84 Hospital San Pedro de Alcantara Cáceres Spain
    85 Hospital de León León Spain
    86 Hospital General Universitario Gregorio Marañon Madrid Spain
    87 Hospital Universitario 12 de Octubre Madrid Spain
    88 Hospital Universitario Ramón Y Cajal Madrid Spain
    89 Hospital Universitario de Salamanca Salamanca Spain
    90 Hospital Universitari i Politecnic La Fe de Valencia Valencia Spain
    91 Sahlgrenska Universitetssjukhuset, Östra sjukhuset Göteborg Sweden
    92 Universitetssjukhuset Örebro Örebro Sweden
    93 Medway NHS Foundation Trust Gillingham United Kingdom
    94 The Leeds Teaching Hospitals NHS Trust Leeds United Kingdom
    95 Chelsea and Westminster Hospital NHS Foundation Trust London United Kingdom
    96 Nottingham University Hospitals NHS Trust Nottingham United Kingdom

    Sponsors and Collaborators

    • Astex Pharmaceuticals, Inc.


    • Study Director: Harold Keer, MD, PhD, Astex Pharmaceuticals, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information


    None provided.
    Responsible Party:
    Astex Pharmaceuticals, Inc. Identifier:
    Other Study ID Numbers:
    • SGI-110-07
    First Posted:
    Sep 20, 2016
    Last Update Posted:
    Sep 5, 2021
    Last Verified:
    Sep 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Plan to Share IPD:
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Sep 5, 2021