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

NCT02907359 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: SGI-110-072015-005257-12
• Study Type: interventional
• Target: 417
• Locations: 14 countries
• Sites: 112

Brief 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.

Conditions

Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  OS was defined as the number of days from the day the participant was randomized to the date of death due to any cause. Survival time was censored on the last date the participant is known alive with no event of death. OS time will be estimated using the Kaplan-Meier method.

  From randomization up to death (up to approximately 38.6 months)

Secondary Outcomes (13)

• Percentage of Participants With Transfusion Independence for Any 8 Consecutive Weeks

  Up to approximately 46.6 months

• Percentage of Participants With Marrow Complete Response (mCR) Along With Transfusion Independence Rate

  Up to approximately 46.6 months

• Survival Rate at 1 Year After Randomization

  From randomization up to 12 months

• Leukemia-free Survival

  From randomization up to 46.6 months

• Number of Days Alive and Out of the Hospital (NDAOH)

  Up to 6 months

Study Arms (2)

Guadecitabine

EXPERIMENTAL

Participants received Guadecitabine 60 mg/m\^2, SC, on Days 1-5 of each 28-day cycle for at least 6 cycles in the absence of unacceptable toxicity or disease progression requiring alternative therapy. Participants received Guadecitabine treatment beyond 6 cycles as long as the participant continued to benefit based on investigator judgment and participant response and tolerability (or up to a maximum of 36 cycles).

Drug: Guadecitabine

Treatment Choice

ACTIVE COMPARATOR

Participants received one of the three treatment choice options: 1. LDAC 20 mg/m\^2 SC/IV once daily for 14 days of each 28-day cycles for at least 4 cycles in absence of disease progression or unacceptable toxicity.Participants who were responding or had stable disease were to continue treatment as per standard institutional practice. 2. Standard IC of a 7+3 regimen:Cytarabine 100-200 mg/m\^2/day given as continuous infusion for 7 days and anthracycline(daunorubicin(45-60 mg)/idarubicin(9-12 mg)/mitoxantrone(8-12 mg)/m\^2) by IV infusion for 3 days of each 28-day cycles. 3. BSC as needed during the treatment included,but was not limited to,blood transfusions(RBCs or platelets),growth factors including erythropoiesis stimulating agents,granulocyte stimulating factors,iron chelating therapy,and broad-spectrum antibiotics and/or antifungals. Duration for treatment choice was as per locally approved prescribing information and institutional standard practice or up to a maximum 30 cycles.

Other: Treatment Choice

Interventions

Guadecitabine DRUG

Also known as: SGI-110

Guadecitabine

Treatment Choice OTHER

* BSC: according to standard/institutional practice; included RBC or platelet transfusions; growth factors, i.e. erythropoiesis stimulating agents, granulocyte stimulating factors, iron chelating therapy; broad spectrum antibiotics and/or antifungals. * LDAC: 20 mg/m\^2 SC or IV once daily (QD) for 14 days in 28-day cycles. Other schedules were allowed per institutional practice. Treatment for ≥4 cycles absent disease progression/toxicity. BSC per institutional/standard practice. * Standard Intensive Chemotherapy: recommended regimen of 7+3 was given as cytarabine 100-200 mg/m\^2/day continuous infusion for 7 days and an anthracycline for 3 days. Anthracyclines per institutional practice included daunorubicin (45-60 mg/m\^2/day) or idarubicin (9-12 mg/m\^2/day) or mitoxantrone (8-12 mg/m\^2/day) by IV infusion. Participants with complete or partial response after IC induction received ≥1 additional cycles with reduced cytotoxic doses then BSC per standard /institutional practice.

Treatment Choice

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult participants ≥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:
• Participant received HMA for at least 6 cycles and was still transfusion dependent.
• Participant received HMA for at least 2 complete cycles and had disease progression prior to Cycle 6 defined as
• i. ≥50% increase in bone marrow blasts from pre-HMA-treatment levels or from nadir post-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 from pre-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:
• Bone marrow blasts \>5% at randomization, OR
• 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 milliliter/minute (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 (a) while receiving treatment with guadecitabine and for at least 3 months after completing treatment and (b) while receiving treatment with LDAC or IC and for at least 6 months after completing treatment or for the duration specified in local prescribing information, whichever is longer.

You may not qualify if:

• Participants who have been diagnosed as having AML with peripheral blood or bone marrow blasts of ≥20%.
• Participants who may still be sensitive to repeated treatment with decitabine or azacitidine such as participants 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 × upper limit of normal (ULN) (except for participants 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 participant 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
• Participants with TP53 mutations

Sponsors & Collaborators

• Astex Pharmaceuticals, Inc.: lead

Study Sites (112)

City of Hope

Duarte, California, 91010, United States

Location

Desert Hematology Oncology Medical Group, Inc.

Rancho Mirage, California, 92270, United States

Location

Cancer Specialists of North Florida

Fleming Island, Florida, 32003, United States

Location

Mount Sinai Medical Center

Miami Beach, Florida, 33140, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

North Shore Medical Center

Evanston, Illinois, 60201, United States

Location

Franciscan Health Indianapolis

Indianapolis, Indiana, 46237, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

University of Michigan Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

John Theurer Cancer Center

Hackensack, New Jersey, 07601, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

Stony Brook University Medical Center

Stony Brook, New York, 11794, United States

Location

Duke Cancer Center

Durham, North Carolina, 27705, United States

Location

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Bon Secours Saint Francis Hospital

Greenville, South Carolina, 29607, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

West Virginia University Mary Babb Randolph Cancer Center

Morgantown, West Virginia, 26506, United States

Location

Ziekenhuis Netwerk Antwerpen Stuivenberg

Antwerp, Belgium

Location

Algemeen Ziekenhuis Sint-Jan Brugge-Oostende

Bruges, Belgium

Location

Grand Hôpital de Charleroi - Notre Dame

Charleroi, Belgium

Location

Tom Baker Cancer Center

Calgary, Alberta, T2N 4N2, Canada

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

Royal Victoria Regional Health Centre

Barrie, Ontario, L4M 6M2, Canada

Location

Juravinski Cancer Centre

Hamilton, Ontario, L8V 1C3, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2C1, Canada

Location

Burnaby Hospital

Burnaby, Canada

Location

Moncton Hospital

Moncton, Canada

Location

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

Montreal, Canada

Location

Saskatchewan Cancer Agency

Regina, Canada

Location

Fakultní nemocnice Brno

Brno, Czechia

Location

Fakultni Nemocnice Hradec Králové

Hradec Králové, Czechia

Location

Fakultní nemocnice Ostrava

Ostrava, Czechia

Location

Fakultní Nemocnice Královské Vinohrady

Prague, Czechia

Location

Onkologická klinika Všeobecná fakultní nemocnice v Praze a 1

Prague, Czechia

Location

Aalborg Universitetshospital

Aalborg, Denmark

Location

Aarhus Universitetshospital

Aarhus, Denmark

Location

Rigshospitalet

Copenhagen, Denmark

Location

Odense University Hospital

Odense, Denmark

Location

Centre Hospitalier Universitaire

La Tronche, France

Location

Hôpital Dupuytren

Limoges, France

Location

GHR Mulhouse Sud-Alsace

Mulhouse, France

Location

Hôpital Hôtel-Dieu

Nantes, France

Location

Centre Antoine Lacassagne

Nice, France

Location

Hôpital Saint Louis

Paris, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, France

Location

Centre Hospitalier Universitaire de Toulouse

Toulouse, France

Location

Städtisches Klinikum Braunschweig

Braunschweig, Germany

Location

Marien Hospital Düsseldorf

Düsseldorf, Germany

Location

Universitaetsklinikum Freiburg

Freiburg im Breisgau, Germany

Location

Universitätsklinikum Halle

Halle, Germany

Location

Universitätsklinikum Ulm

Ulm, Germany

Location

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

Alessandria, Italy

Location

Azienda Ospedaliero Universitaria Careggi

Florence, Italy

Location

Azienda Ospedaliera Universitaria San Martino

Genova, Italy

Location

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, Italy

Location

AORN A. Cardarelli

Napoli, Italy

Location

Azienda Ospedaliera Universitaria-Maggiore della Carità di Novara

Novara, Italy

Location

Azienda Ospedaliera Ospedali Riuniti Marche Nord

Pesaro, Italy

Location

Ospedale S. Eugenio

Roma, Italy

Location

NHO Nagoya Medical Center

Nagoya, Aichi-ken, Japan

Location

Narita Red Cross Hospital

Narita, Chiba, Japan

Location

University of Fukui Hospital

Yoshida, Fukui, Japan

Location

Chugoku Central Hospital

Fukuyama-shi, Hiroshima, Japan

Location

Tokai University Hospital

Isehara, Kanagawa, Japan

Location

Kitasato University Hospital

Sagamihara-shi, Kanagawa, Japan

Location

Yokohama Municipal Citizen's Hospital

Yokohama, Kanagawa, Japan

Location

Nagasaki University Hospital

Nagasaki, Nagasaki-shi, Japan

Location

Kansai Medical University Hirakata

Hirakata, Osaka, Japan

Location

Kindai University Hospital

Osakasayama-shi, Osaka, Japan

Location

Saitama Medical Center

Kawagoe, Saitama, Japan

Location

Nippon Medical School Hospital

Bunkyō-Ku, Tokyo, Japan

Location

The Cancer Institute Hospital of Japanese Foundation for Cancer Research

Koto, Tokyo, Japan

Location

NTT Medical Center Tokyo

Shinagawa, Tokyo, Japan

Location

National Hospital Organization Disaster Medical Center

Tachikawa, Tokyo, Japan

Location

National Hospital Organization Kyushu

Fukuoka, Japan

Location

Fukushima Medical University

Fukushima, Japan

Location

Gifu Municipal Hospital

Gifu, Japan

Location

National Hospital Organization Kumamoto Medical Center

Kumamoto, Japan

Location

Japanese Red Cross Kyoto Daini Hospital

Kyoto, Japan

Location

University Hospital-Kyoto Prefectural University of Medicine

Kyoto, Japan

Location

Yamagata University Hospital

Yamagata, Japan

Location

Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie

Lublin, Poland

Location

Instytut Hematologii i Transfuzjologii

Warsaw, Poland

Location

Samodzielny Publiczny Centralny Szpital Kliniczny

Warsaw, Poland

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Seoul Saint Mary's Hospital

Seoul, 137-701, South Korea

Location

Ulsan University Hospital

Ulsan, 44033, South Korea

Location

Hospital General Universitario de Alicante

Alicante, Spain

Location

Hospital Universitari Germans Trias i Pujol

Badalona, Spain

Location

Fundació Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, Spain

Location

Hospital San Pedro de Alcantara

Cáceres, Spain

Location

Hospital de León

León, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Hospital Universitario Ramón Y Cajal

Madrid, Spain

Location

Hospital Universitario de Salamanca

Salamanca, Spain

Location

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, Spain

Location

Sahlgrenska Universitetssjukhuset, Östra sjukhuset

Gothenburg, Sweden

Location

Universitetssjukhuset Örebro

Örebro, Sweden

Location

Medway NHS Foundation Trust

Gillingham, United Kingdom

Location

The Leeds Teaching Hospitals NHS Trust

Leeds, United Kingdom

Location

Chelsea and Westminster Hospital NHS Foundation Trust

London, United Kingdom

Location

Nottingham University Hospitals NHS Trust

Nottingham, United Kingdom

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic

Interventions

guadecitabine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Taiho Central
• Organization: Taiho Oncology, Inc.

clinicaltrialinfo@taihooncology.com

609-250-7336

Study Officials

• Yuri Sano, MD, PhD

  Astex Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2016
• First Posted: September 20, 2016
• Study Start: January 13, 2017
• Primary Completion: March 31, 2020
• Study Completion: November 30, 2020
• Last Updated: August 27, 2024
• Results First Posted: May 18, 2023

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

DK (4); FR (8); DE (5); IT (8); JP (22); KR (6); BE (3); GB (4); US (22); PL (3); CA (9); ES (11); SE (2); CZ (5)