Clinical trial NCT01261312
Conditions: MDS CMML AML
Keywords: SGI-110 DNA Hypomethylating Agent Intermediate 1, Intermediate 2, CMML or High Risk MDS AML
Sponsor: Astex Pharmaceuticals, Inc.
Start date: 2011-01-04; Completion date: 2016-07-22
Enrollment: 414 participants; Allocation: RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
Phase 1-2 dose-escalation randomized study in participants with intermediate or high risk myelodysplastic syndromes (MDS) or acute myelogenous leukemia (AML). The Dose Escalation Segment will evaluate the biological activity, preliminary safety and efficacy of SGI-110 with two dosing schedules in MDS and AML participants while the Dose Expansion Segment will further evaluate safety and efficacy at the biological effective dose (BED) or maximum tolerated dose (MTD) as defined in the Dose Escalation Segment.

Detailed description:
Once the biologically effective dose (BED) and maximum tolerated dose (MTD) is determined in the Dose Escalation Segment, the Dose Expansion Segment will randomize participants with MDS, treatment naïve elderly acute myeloid leukemia (AML), and relapsed/refractory AML participants to receive the BED or MTD dose. Relapsed/refractory AML participants may also receive SGI-110 on a daily x 10 schedule based on the total dose per cycle evaluated in the Dose-escalation Segment using the 5-daily regimen.

Arms: arm 1: Participants received starting dose of guadecitabine 3 milligrams per meter square (mg/m\^2), subcutaneously (SC), daily from Days 1-5, of a 28-day cycle. The dose was subsequently increased to 9, 18, 36, 60, 90, 125 mg/m\^2 for subsequent cycles until development of toxicity or disease progression. arm 2: Participants received starting dose of guadecitabine 6 mg/m\^2, SC, once weekly on Days 1, 8 and 15, of a 28-day cycle. The dose was subsequently increased to 18, 36, 60, 90, 125 mg/m\^2 for subsequent cycles until development of toxicity or disease progression. arm 3: Participants received starting dose of guadecitabine 60 mg/m\^2, SC, twice weekly on Days 1, 4, 8, 11, 15 and 18, of a 28-day cycle. The dose was subsequently increased to 90 mg/m\^2 for subsequent cycles until development of toxicity or disease progression. arm 4: Participants received guadecitabine 60 mg/m\^2, SC, daily, from Days 1-5, of a 28-day cycle in participants with diagnosis relapsed/refractory (r/r) AML. arm 5: Participants received guadecitabine 90 mg/m\^2, SC, daily, from Days 1-5, of a 28-day cycle in participants with a diagnosis of r/r AML. arm 6: Participants received guadecitabine 60 mg/m\^2, SC, daily from Days 1-5 and 8-12, of a 28-day cycle in participants with a diagnosis of r/r AML. arm 7: Participants received guadecitabine 60 mg/m\^2, SC, daily from Days 1-5, SC of a 28-day cycle in participants with a diagnosis of treatment naïve (TN) AML. arm 8: Participants received guadecitabine 90 mg/m\^2, SC, daily, from Days 1-5, of a 28-day cycle in participants with a diagnosis of TN AML. arm 9: Participants received guadecitabine 60 mg/m\^2, SC, daily from Days 1-5 and 8-12, of a 28-day cycle in participants with a diagnosis of TN AML. arm 10: Participants received guadecitabine 60 mg/m\^2, SC, daily on Days 1-5, of a 28-day cycle in participants with a diagnosis of r/r Myelodysplastic Syndromes (MDS). arm 11: Participants received guadecitabine 90 mg/m\^2, SC, daily on Days 1-5, of a 28-day cycle in participants with a diagnosis of r/r MDS. arm 12: Participants received guadecitabine 60 mg/m\^2, SC, daily on Days 1-5, of a 28-day cycle in participants with a diagnosis of TN MDS. arm 13: Participants received guadecitabine 90 mg/m\^2, SC daily on Days 1-5, of a 28-day cycle in participants with a diagnosis of TN MDS.
Interventions: intervention 1: Guadecitabine
Intervention descriptions: intervention 1: Subcutaneous injection

Protocol documents: