Newly diagnosed Acute Myeloid Leukemia and Intermediate-2, or high-risk Myelodysplastic Syndrome MedDRA version: 9.1 Level: LLT Classification code 10000880 Term: Acute myeloid leukaemia MedDRA version: 9.1 Level: LLT Classification code 10028533 Term: Myelodysplastic syndrome
Conditions
Interventions
Product Name: MGCD0103
Pharmaceutical Form: Capsule, hard
Other descriptive name: N- (2-amino-phenyl)-4-[(4-pyridin-3-yl-pyrimidin-2-ylamino)-methyl] benzamide dihydrob
Sponsors
Pharmion Corporation
MethylGene Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Written informed consent, willingness, and ability to comply with all study procedures; •Pathologic confirmation of newly diagnosed (de novo or untreated secondary) AML or newly diagnosed Int-2 or high-risk MDS (IPSS classification) per WHO criteria; •Age = 60 years; •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2; •Total bilirubin = 1.5 x upper limit of normal (ULN) (unless increased due to Gilbert’s disease or hemolysis); •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ? 2.5 x ULN; •Serum creatinine = 2.0 x ULN; and •Use of adequate contraception when appropriate. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: •Subjects considered fit for intensive chemotherapy who opt to be treated with intensive chemotherapy; •Prior transplantation or any prior anticancer therapy (standard or investigational, including chemotherapy, treatment with HDAC inhibitors, or combination HDAC and azacitidine) administered to treat AML or MDS. Prior treatments with agents such as hydroxyurea or corticosteroids used for peripheral count control will be allowed; •Known or suspected hypersensitivity to any components of MGCD0103 capsules or azacitidine formulation components (eg, mannitol); •Clinical evidence of central nervous system (CNS) involvement by leukemia; •In blast transformation of chronic myeloid leukemia (CML); •A diagnosis of promyelocytic leukemia; •Presence of advanced malignant hepatic tumors; •Any condition that will put the subject at undue risk or discomfort as a result of adherence to study procedures (eg , requirement to take MGCD0103 with low pH beverage); •Previous or concurrent malignancy except the following: adequately treated basal cell or squamous cell skin cancer; in situ carcinoma of the cervix; or other solid tumor treated curatively and without evidence of recurrence for at least 3 years prior to study entry; •Active and uncontrolled clinically significant infection; •History of gastrointestinal hemorrhage within the last 3 months; •Known positive serology for hepatitis B surface antigen, hepatitis C antibody; or human immunodeficiency virus; or •Less than 4 weeks elapsed since any major surgery.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the objective response rate (ORR), defined as the percentage of subjects with a complete remission (CR) or partial remission (PR) to treatment with single-agent azacitidine (Arm A), single-agent MGCD0103 (Arm B), or azacitidine plus MGCD0103 combination therapy (Arm C) in elderly subjects with newly diagnosed acute myelogenous leukemia (AML), or newly diagnosed intermediate 2 (Int 2) or high risk myelodysplastic syndrome (MDS) classified by MDS International Prognostic Scoring System (IPSS) criteria as modified by the International Working Group (IWG). ; Secondary Objective: To determine for each of the 3 treatment arms: •Duration of objective response (CR + PR); •Time to progression; •Progression-free survival; •Overall survival; •Red blood cell (RBC) transfusion independence; •Hematologic improvement (according to International Working Group [IWG] criteria); •Quality of life (QOL); •Safety profile; and •Pharmacokinetics of azacitidine and MGCD0103 when administered as single agents and in combination. Exploratory Correlative Biology Objectives •To assess the prognostic significance of baseline levels of biomarkers isolated from plasma, peripheral blood cells, and/or bone marrow; and •To assess the pharmacodynamic effects of treatment on biomarkers isolated from plasma, peripheral blood cells, and/or bone marrow and correlate these effects with plasma study drug levels and/or treatment outcome. ;Primary end point(s): Overall response rate, as defined by complete or partial remission. | — |
Countries
France, Sweden, United Kingdom
Outcome results
None listed