Myelodysplastic Syndromes (MDS) or Chronic Myelomonocytic Leukemia (CMML)
Conditions
Interventions
investigational material(s)
Generic name etc : Guadecitabine (SGI-110)
INN of investigational material : Guadecitabine
Therapeutic category code : 429 Other antitumor agents
Dosage and Administratio
45-60 mg/m2/day, or idarubicin
9-12 mg/m2/day, or mitoxantrone
8-12 mg/m2/day) for 3 days
Sponsors
Otsuka Pharmaceutical Co., Ltd.
Astex Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Cytologically or histologically confirmed diagnosis of MDS or CMML according to the 2008 World Health Organization (WHO) classification. - ECOG PS of 0-2. - Subjects with 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: a. Subject received HMA for at least 6 cycles and was still transfusion dependent (as defined in 5b below). b. Subject had disease progression prior to Cycle 6 defined as 50% or more increase in bone marrow blasts from pretreatment levels to more than 5%, or 2 g/dL or more reduction of Hgb from pretreatment levels with transfusion dependence after at least 2 cycles of HMA. - Subjects must have either: a. Bone marrow blasts more than 5% at randomization, OR b. 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 or more estimated by the Cockroft-Gault (C-G) or other medically acceptable formulas such as MDRD or CKD-EPI. - 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
Exclusion criteria: - Subjects who have been diagnosed as having acute myeloid leukemia (AML) with peripheral blood or bone marrow blasts of 20% or more. - Subjects who may still be sensitive to repeated treatment with decitabine or azacitidine. - 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 more than 2.5 ULN (except for subjects with Gilbert's Syndrome for whom direct bilirubin is less than 2.5 ULN), or liver cirrhosis or chronic liver disease Child-Pugh Class B or C. - Known active human immunodeficiency virus, hepatitis B virus, or hepatitis C virus infection. - 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 more than 2 liters per minute (LPM) oxygen.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| efficacy Overall Survival (OS): Defined as the number of days from the day the subject was randomized to the date of death (regardless of cause). | — |
Secondary
| Measure | Time frame |
|---|---|
| safety efficacy - Transfusion independence for any 8 consecutive weeks: Number and rate of subjects who are free of transfusions for 8 consecutive weeks (or more) at any time after start of study treatment. - Marrow CR (mCR) with transfusion independence. - Survival rate at 1 year after randomization. - Leukemia-free survival. - Number of days alive and out of the hospital. - Disease response including CR, mCR, PR, and HI: Based on IWG 2006 criteria. - Duration of response. - Number of RBC or platelet transfusions over the duration of the study treatment. - Health-related QOL. - Adverse events. - 30- and 60-day all-cause mortality. | — |
Countries
Asia except Japan, Europe, Japan, North America
Outcome results
None listed