Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02907359
Recruitment Status : Active, not recruiting
First Posted : September 20, 2016
Last Update Posted : June 14, 2019
Sponsor:
Information provided by (Responsible Party):
Astex Pharmaceuticals, Inc. ( Astex Pharmaceuticals )

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
Myelodysplastic Syndromes Leukemia, Myelomonocytic, Chronic Drug: Guadecitabine Other: Treatment Choice 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 408 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 : October 2016
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2020


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 Name: 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.




Primary Outcome Measures :
  1. Overall survival [ Time Frame: 18 Months ]

Secondary Outcome Measures :
  1. Transfusion independence [ Time Frame: 18 months ]
  2. Marrow complete response [ Time Frame: 18 months ]
  3. Survival rate [ Time Frame: 18 months ]
  4. Leukemia-free survival [ Time Frame: 18 months ]
    As described in Time Frame.

  5. Number of days alive and out of the hospital (NDAOH). [ Time Frame: 18 months ]
  6. Disease response [ Time Frame: 18 months ]
  7. Duration of response [ Time Frame: 18 months ]
  8. Number of transfusions [ Time Frame: 18 months ]
  9. Health-related quality of life [ Time Frame: 18 months ]
  10. Incidence and severity of adverse events. [ Time Frame: 18 months ]
  11. 30-day and 60-day all-cause mortality [ Time Frame: 18 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02907359


  Hide Study Locations
Locations
Layout table for location information
United States, California
City of Hope
Duarte, California, United States, 91010
Desert Hematology Oncology Medical Group, Inc.
Rancho Mirage, California, United States, 92270
United States, Florida
Cancer Specialists of North Florida
Fleming Island, Florida, United States, 32003
Mount Sinai Medical Center
Miami Beach, Florida, United States, 33140
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
North Shore Medical Center
Evanston, Illinois, United States, 60201
United States, Indiana
Franciscan Health Indianapolis
Indianapolis, Indiana, United States, 46237
United States, Maryland
University of Maryland
Baltimore, Maryland, United States, 21201
United States, Michigan
University of Michigan Cancer Center
Ann Arbor, Michigan, United States, 48109
United States, New Jersey
John Theurer Cancer Center
Hackensack, New Jersey, United States, 07601
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Weill Cornell Medical College
New York, New York, United States, 10065
Stony Brook University Medical Center
Stony Brook, New York, United States, 11794
United States, North Carolina
Duke Cancer Center
Durham, North Carolina, United States, 27705
United States, Pennsylvania
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
Bon Secours Saint Francis Hospital
Greenville, South Carolina, United States, 29607
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Washington
Swedish Cancer Institute
Seattle, Washington, United States, 98104
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109
United States, West Virginia
West Virginia University Mary Babb Randolph Cancer Center
Morgantown, West Virginia, United States, 26506
Belgium
Ziekenhuis Netwerk Antwerpen Stuivenberg
Antwerp, Belgium
Algemeen Ziekenhuis Sint-Jan Brugge-Oostende
Brugge, Belgium
Grand Hôpital de Charleroi - Notre Dame
Charleroi, Belgium
Canada, Alberta
Tom Baker Cancer Center
Calgary, Alberta, Canada, T2N 4N2
University of Alberta Hospital
Edmonton, Alberta, Canada, T6G 2B7
Canada, Ontario
Royal Victoria Regional Health Centre
Barrie, Ontario, Canada, L4M 6M2
Juravinski Cancer Centre
Hamilton, Ontario, Canada, L8V 1C3
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2C1
Canada
Burnaby Hospital
Burnaby, Canada
Moncton Hospital
Moncton, Canada
Maisonneuve-Rosemont Hôpital Service d'Hematologie et d'Oncologie Medicale
Montréal, Canada
Saskatchewan Cancer Agency
Regina, Canada
Czechia
Fakultní nemocnice Brno
Brno, Czechia
Fakultni Nemocnice Hradec Králové
Hradec Králové, Czechia
Fakultní nemocnice Ostrava
Ostrava, Czechia
Onkologická klinika Všeobecná fakultní nemocnice v Praze a 1
Praha 2, Czechia
Fakultní Nemocnice Královské Vinohrady
Praha, Czechia
Denmark
Aalborg Universitetshospital
Aalborg, Denmark
Aarhus Universitetshospital
Aarhus, Denmark
Rigshospitalet
Copenhagen, Denmark
Odense University Hospital
Odense, Denmark
France
Centre Hospitalier Universitaire
La Tronche, France
Hôpital Dupuytren
Limoges, France
GHR Mulhouse Sud-Alsace
Mulhouse Cedex, France
Hôpital Hôtel-Dieu
Nantes, France
Centre Antoine Lacassagne
Nice, France
Hôpital Saint Louis
Paris, France
Centre Hospitalier Lyon Sud
Pierre-Bénite, France
Centre Hospitalier Universitaire de Toulouse
Toulouse, France
Germany
Städtisches Klinikum Braunschweig
Braunschweig, Germany
Marien Hospital Düsseldorf
Düsseldorf, Germany
Universitaetsklinikum Freiburg
Freiburg, Germany
Universitätsklinikum Halle
Halle, Germany
Universitätsklinikum Ulm
Ulm, Germany
Italy
Azienda Ospedaliera SS. Antonio E. Biagio E. Cesare Arrigo di Alessandria
Alessandria, Italy
Azienda Ospedaliero Universitaria Careggi
Firenze, Italy
Azienda Ospedaliera Universitaria San Martino
Genova, Italy
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milano, Italy
AORN A. Cardarelli
Napoli, Italy
Azienda Ospedaliera Universitaria-Maggiore della Carità di Novara
Novara, Italy
Azienda Ospedaliera Ospedali Riuniti Marche Nord
Pesaro, Italy
Ospedale S. Eugenio
Roma, Italy
Japan
Chubu, Japan
Chugoku, Japan
Kanto, Japan
Kinki, Japan
Kyushu, Japan
Tohoku, Japan
Korea, Republic of
Seoul National University Hospital
Seoul, Korea, Republic of, 03080
Severance Hospital, Yonsei University Health System
Seoul, Korea, Republic of, 03722
Asan Medical Center
Seoul, Korea, Republic of, 05505
Samsung Medical Center
Seoul, Korea, Republic of, 06351
Seoul Saint Mary's Hospital
Seoul, Korea, Republic of, 137-701
Ulsan University Hospital
Ulsan, Korea, Republic of, 44033
Poland
Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
Lublin, Poland
Instytut Hematologii i Transfuzjologii
Warszawa, Poland
Samodzielny Publiczny Centralny Szpital Kliniczny
Warszawa, Poland
Spain
Hospital General Universitario de Alicante
Alicante, Spain
Hospital Universitari Germans Trias i Pujol
Badalona, Spain
Fundació Hospital de la Santa Creu i Sant Pau
Barcelona, Spain
Hospital Universitario Vall d'Hebron
Barcelona, Spain
Hospital San Pedro de Alcantara
Cáceres, Spain
Hospital de León
León, Spain
Hospital General Universitario Gregorio Marañon
Madrid, Spain
Hospital Universitario 12 de Octubre
Madrid, Spain
Hospital Universitario Ramón Y Cajal
Madrid, Spain
Hospital Universitario de Salamanca
Salamanca, Spain
Hospital Universitari i Politecnic La Fe de Valencia
Valencia, Spain
Sweden
Sahlgrenska Universitetssjukhuset, Östra sjukhuset
Göteborg, Sweden
Universitetssjukhuset Örebro
Örebro, Sweden
United Kingdom
Medway NHS Foundation Trust
Gillingham, United Kingdom
The Leeds Teaching Hospitals NHS Trust
Leeds, United Kingdom
Chelsea and Westminster Hospital NHS Foundation Trust
London, United Kingdom
Nottingham University Hospitals NHS Trust
Nottingham, United Kingdom
Sponsors and Collaborators
Astex Pharmaceuticals
Investigators
Layout table for investigator information
Study Director: Harold Keer, MD, PhD Astex Pharmaceuticals, Inc.

Layout table for additonal information
Responsible Party: Astex Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02907359     History of Changes
Other Study ID Numbers: SGI-110-07
First Posted: September 20, 2016    Key Record Dates
Last Update Posted: June 14, 2019
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia
Preleukemia
Leukemia, Myelomonocytic, Chronic
Myelodysplastic Syndromes
Syndrome
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Leukemia, Myeloid
Myelodysplastic-Myeloproliferative Diseases
Azacitidine
Guadecitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors