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

Completed · Phase 3

Conditions studied: Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic

In brief

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.

Key facts

Study ID

NCT02907359

Run by

Astex Pharmaceuticals, Inc.

People needed

417

Starts

2017-01-13

Expected to finish

2020-11-30

Last updated by the study team

2024-08-27

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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

Where it is running

• Desert Hematology Oncology Medical Group, Inc. — Rancho Mirage, California, United States
• Cancer Specialists of North Florida — Fleming Island, Florida, United States
• Mount Sinai Medical Center — Miami Beach, Florida, United States
• Rush University Medical Center — Chicago, Illinois, United States
• North Shore Medical Center — Evanston, Illinois, United States
• Franciscan Health Indianapolis — Indianapolis, Indiana, United States
• University of Maryland — Baltimore, Maryland, United States
• University of Michigan Cancer Center — Ann Arbor, Michigan, United States
• John Theurer Cancer Center — Hackensack, New Jersey, United States
• Roswell Park Cancer Institute — Buffalo, New York, United States
• Weill Cornell Medical College — New York, New York, United States
• Stony Brook University Medical Center — Stony Brook, New York, United States
• Duke Cancer Center — Durham, North Carolina, United States
• Penn State Milton S. Hershey Medical Center — Hershey, Pennsylvania, United States
• Fox Chase Cancer Center — Philadelphia, Pennsylvania, United States
• Medical University of South Carolina — Charleston, South Carolina, United States
• Bon Secours Saint Francis Hospital — Greenville, South Carolina, United States
• University of Texas MD Anderson Cancer Center — Houston, Texas, United States
• Swedish Cancer Institute — Seattle, Washington, United States
• Fred Hutchinson Cancer Research Center — Seattle, Washington, United States
• West Virginia University Mary Babb Randolph Cancer Center — Morgantown, West Virginia, United States
• Ziekenhuis Netwerk Antwerpen Stuivenberg — Antwerp, Belgium
• Algemeen Ziekenhuis Sint-Jan Brugge-Oostende — Bruges, Belgium
• Grand Hôpital de Charleroi - Notre Dame — Charleroi, Belgium
• City of Hope — Duarte, California, United States

Full record on ClinicalTrials.gov

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