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
The goal of this clinical research study is to compare the safety and effectiveness of the study drug SGI-110 (guadecitabine) to current standard treatment.
Disease Group: Malignant neoplasms stated as primary lymphoid haematopoietic
Treatment Agent: SGI-110
Treatment Location: Both at MD Anderson & Other Sites
Sponsor: Astex Pharmaceuticals
Primary Objective To assess and compare overall survival (OS) between guadecitabine and treatment choice (TC) in adults with myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) previously treated with a hypomethylating agent (HMA) (azacitidine [AZA] or decitabine [DAC], or both). Secondary Objectives To assess and compare effects of guadecitabine and TC in adults with MDS or CMML previously treated with a hypomethylating agent (azacitidine or decitabine, or both) with respect to the following variables: Transfusion independence. Marrow complete response (mCR) with transfusion independence. Survival rate at 1 year after randomization. Leukemia-free survival. Number of days alive and out of the hospital (NDAOH). Disease response based on IWG 2006 MDS criteria including complete response (CR), partial response (PR), mCR, and hematological improvement (HI erythroid, platelet, or neutrophil response) and duration of response. Number of red blood cell (RBC) and platelet transfusions. Health-related quality of life (QOL). Safety. Exploratory Objectives To assess influence of demographic characteristics, disease characteristics, and molecular biomarkers on treatment outcomes. To evaluate pharmacokinetic (PK) exposure-response relationships with efficacy and safety parameters.
IRB Review and Approval Date: 02/23/2017
Recruitment Status: Open
Projected Accrual: 408
1) 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.
2) Cytologically or histologically confirmed diagnosis of MDS or CMML according to the 2008 World Health Organization (WHO) classification.
3) Performance status (ECOG) of 0-2.
4) Subjects with previously treated MDS or CMML, defined as prior treatment with at least one 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% increase in bone marrow blasts from pretreatment levels to >5% or >/= 2g/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.
5) Subjects must have either: a) Bone marrow blasts >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.
6) 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).
7) Women of child-bearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. Women of child-bearing potential and men with female partners of child-bearing 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.
1) Subjects who have been diagnosed as having AML with peripheral blood
or bone marrow blasts of >/=20%.
2) 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.
3) Prior treatment with guadecitabine.
4) Hypersensitivity to decitabine, guadecitabine, or any of their excipients.
5) Second malignancy currently requiring active therapy, except breast or prostate cancer stable on or responding to endocrine therapy.
6) Treated with any investigational drug within 2 weeks of the first dose of study treatment.
7) 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.
8) Known active human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection. Inactive hepatitis carrier status or low viral hepatitis titer on antivirals is allowed.
9) 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.
10) 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 (LPM) oxygen.
Information and next steps
Malignant neoplasms stated as primary lymphoid haematopoietic
For general questions about clinical trials: