A Phase 3, Multicenter, Randomized, Open-Label Study of Guadecitabine (SGI-110) versus Treatment Choice in Adults with Previously Treated Acute Myeloid Leukemia
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: Cytarabine,Decitabine,Fludarabine,G-CSF,Guadecitabine,Idarubicin
Treatment Location: Both at MD Anderson & Other Sites
Sponsor: Astex Pharmaceuticals, Inc.
Primary Objective To assess and compare overall survival (OS) between guadecitabine and treatment choice (TC) in adults with previously treated acute myeloid leukemia (AML). Secondary Objectives To assess and compare effects of guadecitabine and TC in adults with previously treated AML with respect to the following variables: Event-free survival (EFS). Long-term survival. Number of days alive and out of the hospital (NDAOH). Transfusion needs. Complete response (CR) rate. Composite CR rate (CRc). CRc = CR + CR with incomplete blood count recovery (CRi) + CR with incomplete platelet recovery (CRp). Bridge to hematopoietic cell transplant (HCT). Health-related quality of life (QOL). Safety. Exploratory Objectives To assess influence of demographics, 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: 06/29/2017
Recruitment Status: Open
Projected Accrual: 404
1) Adult subjects >/=18 years of age who are able to understand study
procedures, comply with them, and provide written informed consent
before any study-specific procedure.
2) History of cytologically or histologically confirmed diagnosis of AML (except acute promyelocytic leukemia) according to the 2008 World Health Organization (WHO) classification (BM or PB blast counts >/=20%).
3) Performance status (ECOG) of 0-2.
4) Subjects with AML previously treated with initial induction therapy using a standard intensive chemotherapy regimen, including cytarabine and an anthracycline, and who are refractory to initial induction (primary refractory) or in relapse after such initial induction.
5) Subjects must have either PB or BM blasts >/=5% at time of randomization.
6) Creatinine clearance or glomerular filtration rate >/=30 mL/min as 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 any study therapy and for at least 3 months after completing treatment.
1) Known clinically active CNS or extramedullary AML, except leukemia cutis.
2) Subjects in first relapse after initial induction who had a response duration >12 months OR favorable cytogenetics since those subjects may benefit from re-induction with the same or similar prior regimen.
3) BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis).
4) Second malignancy currently requiring active therapy, except breast or prostate cancer stable on or responding to endocrine therapy.
5) Grade 3 or higher Graft Versus Host Disease (GVHD), or GVHD on either a calcineurin inhibitor or prednisone more than 5 mg/day.
6) Prior treatment with decitabine, azacitidine, or guadecitabine.
7) Hypersensitivity to decitabine, guadecitabine, or any of their excipients.
8) Treated with any investigational therapy within 2 weeks of the first dose of study treatment.
9) Total serum bilirubin >2.5 × upper limit of normal (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.
10) 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.
11) 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.
12) Refractory congestive heart failure unresponsive to medical treatment; active infection resistant to all antibiotics; or non-AML-associated pulmonary disease requiring >2 liters per minute (LPM) oxygen.
Information and next steps
Malignant neoplasms stated as primary lymphoid haematopoietic
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