SGI-110 in Participants With Myelodysplastic Syndromes (MDS) or Acute Myelogenous Leukemia (AML)

A Phase 1-2, Dose Escalation, Multicenter Study of Two Subcutaneous Regimens of SGI-110, a DNA Hypomethylating Agent, in Subjects With Intermediate or High-Risk Myelodysplastic Syndromes (MDS) or Acute Myelogenous Leukemia (AML)

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.

Study Overview

• Status: Completed
• Conditions: AML; MDS; CMML
• Intervention / Treatment: Drug: Guadecitabine

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.

• Study Type: Interventional
• Enrollment (Actual): 414
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hospital
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University
  • Florida
    • Fort Myers, Florida, United States, 33916
      • Florida Cancer Specialists - South
    • Saint Petersburg, Florida, United States, 33705
      • Florida Cancer Specialists - North
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Cancer Center
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10021
      • Cornell University
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Temple University
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Men or women, 18 years of age or older, with a confirmed diagnosis of international prognostic scoring system (IPSS) intermediate-1, intermediate-2 or high-risk MDS including Chronic Myelomonocytic Leukemia (CMML) or AML.

   • In the Dose Escalation Segment, participants who are refractory, relapsed, or unresponsive to standard treatment.

   • In the Dose Expansion Segment, hypomethylating agent (HMA) treatment-naïve MDS participants (including CMML), and intermediate-2 or high-risk MDS participant (including CMML) relapsed or refractory to prior HMA treatment are allowed, and treatment-naïve AML participants who is at least 65 years of age will be allowed if they also have at least one of the following criteria

     • AML secondary to MDS, chemotherapy, or radiation therapy
     • poor cytogenetics
     • pre-existing clinically significant dysfunction of the heart or Chronic Obstructive Pulmonary Disease (COPD)
     • poor performance status, Eastern Cooperative Oncology Group (ECOG), of 2
2. Eastern ECOG performance status of 0 to 2.
3. Adequate organ function.
4. Prior allogeneic stem cell transplant, no evidence of active graft-versus host disease (GVHD) and must be ≥ 2 weeks off immunosuppressive therapy.
5. No major surgery within 4 weeks of first dose of SGI-110.
6. No chemotherapy within 2 weeks of first dose of SGI-110 (minimum of 6 weeks for nitrosoureas and 8 weeks for bone marrow transplantation) with the exception of hydroxyurea which will be allowed during course 1 of treatment.
7. Sign an approved informed consent form for this study.

Exclusion Criteria:

1. In the Dose Expansion Segment, which includes the 10-day regimen, participants who have received 2 complete full dose cycles or more of a hypomethylating agent (HMA) decitabine or azacitidine (except for intermediate-2 or high-risk MDS participant (including CMML) relapsed or refractory to prior HMA treatment).
2. Acute promyelocytic leukemia (M3 classification).
3. Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the participant has been disease free for at least 3 years.
4. Life-threatening illnesses other than AML or MDS, uncontrolled medical conditions or organ system dysfunction which, in the investigator's opinion, could compromise the participant's safety, or put the study outcomes at risk.
5. Known history of human immunodeficiency virus (HIV) or active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV).
6. Hypersensitivity to decitabine, SGI-110, or SGI-110 excipients.
7. With the exception of treatment-naïve elderly AML participants, participants with uncontrolled congestive heart failure (CHF), coronary heart disease (CAD), chronic obstructive pulmonary disease (COPD), or left ventricular ejection fraction (LVEF) of ≤ 50% are excluded, symptomatic or uncontrolled arrhythmias or on continuous corticosteroids.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

13

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation: Regimen 1 - Guadecitabine 3 mg/m^2 Daily; 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.	Drug: Guadecitabine; Subcutaneous injection; Other Names: SGI-110
Experimental: Dose Escalation: Regimen 2A - Guadecitabine 6 mg/m^2 Once Weekly; 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.	Drug: Guadecitabine; Subcutaneous injection; Other Names: SGI-110
Experimental: Dose Escalation: Regimen 2B - Guadecitabine 60 mg/m^2 Twice Weekly; 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.	Drug: Guadecitabine; Subcutaneous injection; Other Names: SGI-110
Experimental: Dose Expansion: r/r AML Guadecitabine 60 mg/m^2 (5-Day); 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.	Drug: Guadecitabine; Subcutaneous injection; Other Names: SGI-110
Experimental: Dose Expansion: r/r AML Guadecitabine 90 mg/m^2 (5-Day); 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.	Drug: Guadecitabine; Subcutaneous injection; Other Names: SGI-110
Experimental: Dose Expansion: r/r AML Guadecitabine 60 mg/m^2 (10-Day); 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.	Drug: Guadecitabine; Subcutaneous injection; Other Names: SGI-110
Experimental: Dose Expansion: TN AML Guadecitabine 60 mg/m^2 (5-Day); 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.	Drug: Guadecitabine; Subcutaneous injection; Other Names: SGI-110
Experimental: Dose Expansion: TN AML Guadecitabine 90 mg/m^2 (5-Day); 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.	Drug: Guadecitabine; Subcutaneous injection; Other Names: SGI-110
Experimental: Dose Expansion: TN AML Guadecitabine 60 mg/m^2 (10-Day); 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.	Drug: Guadecitabine; Subcutaneous injection; Other Names: SGI-110
Experimental: Dose Expansion: r/r MDS Guadecitabine 60 mg/m^2 (5-Day); 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).	Drug: Guadecitabine; Subcutaneous injection; Other Names: SGI-110
Experimental: Dose Expansion: r/r MDS Guadecitabine 90 mg/m^2 (5-Day); 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.	Drug: Guadecitabine; Subcutaneous injection; Other Names: SGI-110
Experimental: Dose Expansion: TN MDS Guadecitabine 60 mg/m^2 (5-Day); 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.	Drug: Guadecitabine; Subcutaneous injection; Other Names: SGI-110
Experimental: Dose Expansion: TN MDS Guadecitabine 90 mg/m^2 (5-Day); 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.	Drug: Guadecitabine; Subcutaneous injection; Other Names: SGI-110

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Escalation Phase- Biological Effective Dose (BED): Percent Change From Baseline in DNA Long Interspersed Nucleotide Element-1 (LINE-1) Demethylation	DNA LINE-1 demethylation is defined as the largest percent decrease from baseline in methylation values within a participant between Day 8 and Day 22 of the first treatment cycle. BED was assessed based on DNA LINE-1 demethylation results and defined as the smallest dose that achieves the maximum biological pharmacodynamic (PD) effect (LINE-1 demethylation) in at least 3 successive dose levels.	Cycle 1 Day 8
Dose Escalation Phase- Biological Effective Dose (BED): Percent Change From Baseline in DNA Long Interspersed Nucleotide Element-1 (LINE-1) Demethylation	DNA LINE-1 demethylation is defined as the largest percent decrease from baseline in methylation values within a participant between Day 8 and Day 22 of the first treatment cycle. BED was assessed based on DNA LINE-1 demethylation results and defined as the smallest dose that achieves the maximum biological pharmacodynamic (PD) effect (LINE-1 demethylation) in at least 3 successive dose levels.	Cycle 1 Day 15
Dose Escalation Phase- Biological Effective Dose (BED): Percent Change From Baseline in DNA Long Interspersed Nucleotide Element-1 (LINE-1) Demethylation	DNA LINE-1 demethylation is defined as the largest percent decrease from baseline in methylation values within a participant between Day 8 and Day 22 of the first treatment cycle. BED was assessed based on DNA LINE-1 demethylation results and defined as the smallest dose that achieves the maximum biological pharmacodynamic (PD) effect (LINE-1 demethylation) in at least 3 successive dose levels.	Cycle 1 Day 22
Dose Escalation Phase- Biological Effective Dose (BED): Percent Change From Baseline in DNA Long Interspersed Nucleotide Element-1 (LINE-1) Demethylation	DNA LINE-1 demethylation is defined as the largest percent decrease from baseline in methylation values within a participant between Day 8 and Day 22 of the first treatment cycle. BED was assessed based on DNA LINE-1 demethylation results and defined as the smallest dose that achieves the maximum biological pharmacodynamic (PD) effect (LINE-1 demethylation) in at least 3 successive dose levels.	Cycle 2 Day 1
Dose Escalation Phase-Maximum Tolerated Dose (MTD): Number of Participants With Dose Limiting Toxicity (DLT)	The MTD was defined as the largest dose for which less than 33% of subjects experienced a dose limiting toxicity (DLT) during Cycle 1 of guadecitabine administration at each dose level. DLTs were defined using the Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0).	From the start of study treatment up to 30 days post treatment (Up to approximately 46 months)
Dose Expansion (DE) Phase- r/r AML, TN AML: Composite Complete Response (CRc) Rate	Composite complete response (CRc) rate is defined as the percentage of participants whose best response is complete remission [CR], CR with incomplete platelet recovery [CRp], or CR with incomplete hematological recovery [CRi]) after treatment with study drug. CR as per AML response criteria is defined as peripheral blood absolute neutrophil count (ANC) ≥1.0×10^9/L, Platelets ≥100×10^9/L, independence from red blood cell (RBC) and platelet transfusions over the past week, no myeloblasts and <5% myeloblasts in bone marrow. CRp as per AML response criteria is defined as peripheral blood ANC ≥1.0×10^9/L, Platelets <100×10^9/L, independence from RBC transfusions over the past week, no myeloblasts and <5% myeloblasts in bone marrow. CRi as per AML response criteria is defined as peripheral blood ANC <1.0×10^9/L, no myeloblasts and <5% myeloblasts in bone marrow.	At end of each Cycle of 28 days (Up to approximately 38 months)
Dose Expansion (DE) Phase- r/r MDS, TN MDS: Overall Response Rate (ORR)	ORR is defined as percentage of participants with complete response(CR), partial response(PR), marrow complete response(mCR) and haematological improvement(HI). CR:normal peripheral counts with persistent granulocyte count ≥1.0×10^9/L, platelet count ≥100×10^9/L and normal bone marrow (BM) with persistent marrow blasts ≤5%; persistent dysplasia was noted. PR:normal peripheral counts with granulocyte count ≥1.0×10^9/L and platelet count ≥100 ×10^9/L and normal BM with marrow blasts >5% but were reduced by 50% or more. mCR:reduction of BM blasts to ≤5% without normalization of peripheral counts. HI is divided as erythroid response(HI-E): hemoglobin increase ≥1.5 g/dL or red blood cells transfusion independence, platelet response (HI-P): absolute increase of platelet count from <20 to >20×10^9/L and by at least 100%,/if more than 20×10^9/L, by an absolute increase of 30×10^9/L, neutrophil response (HI-N): granulocyte increase ≥100%, and by an absolute increase ≥0.5×10^9/L.	At end of each Cycle of 28 days (Up to approximately 45 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Escalation Phase: Response Rate in AML Participants	Response rate for AML participants was assessed by Modified International Working Group (IWG) 2003 response criteria with complete response (CR), complete response with incomplete platelet recovery (CRp), CR with incomplete blood count recovery(CRi), and partial response (PR). CR: absolute neutrophil count (ANC) >1.0×10^9/L, platelets ≥100×10^9/L, independence from RBC and platelet transfusions, no or <5% myeloblasts in bone marrow(BM). CRp: ANC >1.0×10^9/L, Platelets <100×10^9/L, independence from RBC transfusions, no or <5% myeloblasts in BM. CRi: ANC <1.0×10^9/L, no or <5% myeloblasts in BM. PR: ANC >1.0×10^9/L, Platelets ≥100×10^9/L, no or decrease of ≥50% in myeloblasts to 5-25% in BM.	At end of each Cycle of 28 days (Up to approximately 23 months)
Dose Escalation Phase: Response Rate in MDS Participants	Response rate for MDS participants was assessed by IWG 2006 Response Criteria with CR, PR, marrow complete response(mCR) and HI. CR: normal peripheral counts with persistent granulocyte count ≥1.0×10^9/L, platelet count ≥100×10^9/L; normal BM with persistent marrow blasts ≤5%; persistent dysplasia. PR: Normal peripheral counts with granulocyte count ≥1.0×10^9/L, platelet count ≥100×10^9/L and normal BM with blasts >5% but reduced by 50% or more. mCR: reduction of BM blasts to ≤5% without normalization of peripheral counts.	At end of each Cycle of 28 days (Up to approximately 23 months)
Dose Escalation and Dose Expansion Phase- r/r AML, TN AML: Duration of Response	Duration of response (in number of days) was calculated from the first time a complete response (CR, CRp, or CRi) was observed to time of relapse defined as the earliest time point whereby BM blasts or peripheral blood blasts become ≥5% and stayed at that level in subsequent visits while participants were still on study. CR:normal peripheral counts with persistent granulocyte count ≥1.0×10^9/L, platelet count ≥100×10^9/L and normal bone marrow (BM) with persistent marrow blasts ≤5%; persistent dysplasia was noted. CRp as per AML response criteria is defined as peripheral blood ANC ≥1.0×10^9/L, Platelets <100×10^9/L, independence from RBC transfusions over the past week, no myeloblasts and <5% myeloblasts in bone marrow. CRi as per AML response criteria is defined as peripheral blood ANC <1.0×10^9/L, no myeloblasts and <5% myeloblasts in bone marrow.	At end of each Cycle of 28 days (Up to approximately 38 months)
Dose Escalation Phase: Hematologic Improvement Rate in MDS		At end of each Cycle of 28 days (Up to approximately 45 months)
DE Phase- r/r MDS, TN MDS: Duration of Response	DOR was calculated from first time a response category (CR, PR, mCR, or HI) was achieved until response category was no longer met or the last available time point, whichever occurred first. CR:normal peripheral counts with persistent granulocyte count ≥1.0×10^9/L, platelet count ≥100×10^9/L and normal bone marrow (BM) with persistent marrow blasts ≤5%; persistent dysplasia was noted. PR:normal peripheral counts with granulocyte count ≥1.0×10^9/L and platelet count ≥100 ×10^9/L and normal BM with marrow blasts >5% but were reduced by 50% or more. mCR:reduction of BM blasts to ≤5% without normalization of peripheral counts. HI is divided as erythroid response(HI-E): hemoglobin increase ≥1.5 g/dL or RBC transfusion independence, platelet response (HI-P): absolute increase of platelet count from <20 to >20×10^9/L by at least 100%,/if more than 20×10^9/L, by absolute increase of 30×10^9/L, neutrophil response (HI-N): granulocyte increase ≥100%, by an absolute increase ≥0.5×10^9/L.	At end of each Cycle of 28 days (Up to approximately 45 months)
Dose Escalation r/r AML, TN AML: Time to Response	Time to response was defined as the number of days from the day a participants received the first dose of guadecitabine (cycle 1 day 1 {C1D1}) to the first day of response. Composite complete response rate (CRc = CR + CRp + CRi), which is an overall complete response assessment including CR, CR with incomplete platelet recovery (CRp) and CR with incomplete blood count recovery (CRi). CRc rate, was defined as the number of participants who achieved a response status of CR, CRp, or CRi divided by the total number of participants included in the efficacy dataset. The CR rate is defined as the number of participants whose best response is CR divided by the total number of participants included in the efficacy dataset.	At end of each Cycle of 28 days (Up to approximately 38 months)
Dose Expansion Phase- r/r MDS, TN MDS: Time to Response	Time to response was defined as the number of days from the day a participants received the first dose of guadecitabine (C1D1) to the first day of response. CR:normal peripheral counts with persistent granulocyte count ≥1.0×10^9/L, platelet count ≥100×10^9/L and normal bone marrow (BM) with persistent marrow blasts ≤5%; persistent dysplasia was noted. PR:normal peripheral counts with granulocyte count ≥1.0×10^9/L and platelet count ≥100 ×10^9/L and normal BM with marrow blasts >5% but were reduced by 50% or more. mCR:reduction of BM blasts to ≤5% without normalization of peripheral counts. HI is divided as erythroid response(HI-E): hemoglobin increase ≥1.5 g/dL or RBC transfusion independence, platelet response (HI-P): absolute increase of platelet count from <20 to >20×10^9/L by at least 100%,/if more than 20×10^9/L, by absolute increase of 30×10^9/L, neutrophil response (HI-N): granulocyte increase ≥100%, by an absolute increase ≥0.5×10^9/L.	At end of each Cycle of 28 days (Up to approximately 45 months)
Number of Participants With Dose Limiting Toxicities (DLT) Assessed Per Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0	DLT was defined using CTCAE v4.0. Toxicities were considered related to SGI-110 if it cannot be explained by underlying disease, intercurrent illness or concomitant medications. Any related Grade 3 or 4 non-hematologic toxicity except Grade 3 or 4 nausea/vomiting that is controllable by anti-emetics or diarrhea controllable by optimal therapy. Grade 3 laboratory investigations other than serum creatinine, bilirubin, AST or ALT were not considered a DLT unless they are associated with clinical manifestations. Study-drug related Grade 4 thrombocytopenia and Febrile neutropenia that was not present at study entry, and not resolve within 7 days, and is not related to underlying disease. Prolonged myelosuppression or pancytopenia with hypocellular bone marrow and no marrow blasts lasting for 6 weeks or more that is not related to disease progression. Any toxicity that results in treatment delays of > 4 weeks. Data is reported for any AE occurring during Cycle 1 (each cycle = 28 days).	Cycle 1 (each cycle = 28 days)
Dose Escalation and Dose Expansion Phases- r/r AML, TN AML, r/r MDS, TN MDS: Number of Participants With At Least One Treatment-Emergent Adverse Events (TEAEs)	Treatment-emergent AEs are defined as events that first occurred or worsened after the first dose of study drug given on C1D1 until 30 days after the last dose of study treatment or the start of an alternative anti-cancer treatment for MDS/CMML and subsequent AML, whichever occurs first, with the following exceptions: events that occurred after 30 days beyond the last dose of study treatment or the start of an alternative anti-cancer treatment for MDS/CMML and subsequent AML was considered treatment-emergent if the events are both serious and related to the study treatment.	From first dose of study drug up 30 days post treatment (up to approximately 46 months)
Dose Escalation and DE Phases- r/r AML, TN AML, r/r MDS, TN MDS: Number of Participants With Abnormal Laboratory Values Reported as Adverse Events		From first dose of study drug up 30 days post treatment (up to approximately 46 months)
Dose Escalation: Maximum Observed Plasma Concentration (Cmax ) of SGI-110 and Decitabine		Days 1, 5 and 8
Dose Escalation: Minimum Observed Plasma Concentration (Cmin)		Days 5 and 8
Dose Escalation: Area Under the Curve to Infinity (AUC0-inf)		Days 1, 5 and 8
Dose Escalation and DE Phase- r/r MDS, TN MDS: Time to AML or Death	Time to AML or death was defined as the number of days from the date the subject received the first dose of guadecitabine (C1D1) to the date of death or the date of MDS/ chronic myelomonocytic leukemia (CMML) progression to AML, whichever occurred earlier. Time to AML or death was evaluated using the Kaplan-Meier method, with the time censored on the last date of contact if a participant was still alive without progression to AML.	At end of each Cycle of 28 days (Up to approximately 38 months)
Dose Escalation and DE Phases- r/r AML, TN AML, r/r MDS, TN MDS: Overall Survival	OS was defined as the number of days from the day the participant received the first dose of guadecitabine to the date of death (regardless of cause).	At end of each Cycle of 28 days (Up to approximately 45 months)
Dose Escalation: Number of Participants Achieving Blood and Platelet Transfusions		Cycle 1, Day 1 through 30 days after the last dose of study drug (up to approximately 46 months)
DE Phase- r/r AML, TN AML: Percentage of Participants With Cr, CRp and PR	CR is defined absolute neutrophil count (ANC) >1.0×109/L, Platelets ≥100×109/L, independence from RBC and platelet transfusions over the past week, no myeloblasts and <5% myeloblasts in bone marrow. CRp is defined ANC >1.0×10^9/L, Platelets <100×10^9/L, independence from RBC transfusions over the past week, no myeloblasts and <5% myeloblasts in bone marrow. CRi is defined as ANC <1.0×10^9/L, no myeloblasts and <5% myeloblasts in bone marrow. PR is defined as ANC >1.0×10^9/L, Platelets ≥100×10^9/L, no myeloblasts and Decrease of ≥50% in myeloblasts to level of 5% to 25% in bone marrow.	At end of each Cycle of 28 days (Up to approximately 45 months)
DE Phase- r/r MDS, TN MDS: Percentage of Participants With CR, PR, mCR and HI	CR is defined ANC >1.0×109/L, Platelets ≥100×109/L, independence from RBC and platelet transfusions over the past week, no myeloblasts and <5% myeloblasts in bone marrow. CRp is defined ANC >1.0×10^9/L, Platelets <100×10^9/L, independence from RBC transfusions over the past week, no myeloblasts and <5% myeloblasts in bone marrow. CRi is defined as ANC <1.0×10^9/L, no myeloblasts and <5% myeloblasts in bone marrow. PR is defined as ANC >1.0×10^9/L, Platelets ≥100×10^9/L, no myeloblasts and Decrease of ≥50% in myeloblasts to level of 5% to 25% in bone marrow.	At end of each Cycle of 28 days (Up to approximately 45 months)
DE Phase- r/r MDS, TN MDS: Number of Participants Achieving Blood Transfusion Independence for 8 or 16-weeks	Transfusion dependence at baseline was defined as any transfusion within 4 weeks of the first study dose (C1D1) with C1D1 transfusion counted, assuming it was always done before dosing. Transfusion independence after treatment was defined as no transfusion within an 8-week or 16-week period between C1D1 and last treatment date + 30 days.	Weeks 8 and 16
DE Phase- r/r MDS, TN MDS: Number of Participants Achieving Platelet Transfusion Independence for 8 or 16-weeks	Transfusion dependence at baseline was defined as any transfusion within 4 weeks of the first study dose (C1D1) with C1D1 transfusion counted, assuming it was always done before dosing. Transfusion independence after treatment was defined as no transfusion within an 8-week or 16-week period between C1D1 and last treatment date + 30 days.	Weeks 8 and 16

Collaborators and Investigators

• Sponsor: Astex Pharmaceuticals, Inc.

Publications and helpful links

General Publications

• Chung W, Kelly AD, Kropf P, Fung H, Jelinek J, Su XY, Roboz GJ, Kantarjian HM, Azab M, Issa JJ. Genomic and epigenomic predictors of response to guadecitabine in relapsed/refractory acute myelogenous leukemia. Clin Epigenetics. 2019 Jul 22;11(1):106. doi: 10.1186/s13148-019-0704-3.
• Garcia-Manero G, Roboz G, Walsh K, Kantarjian H, Ritchie E, Kropf P, O'Connell C, Tibes R, Lunin S, Rosenblat T, Yee K, Stock W, Griffiths E, Mace J, Podoltsev N, Berdeja J, Jabbour E, Issa JJ, Hao Y, Keer HN, Azab M, Savona MR. Guadecitabine (SGI-110) in patients with intermediate or high-risk myelodysplastic syndromes: phase 2 results from a multicentre, open-label, randomised, phase 1/2 trial. Lancet Haematol. 2019 Jun;6(6):e317-e327. doi: 10.1016/S2352-3026(19)30029-8. Epub 2019 May 3.
• Issa JJ, Roboz G, Rizzieri D, Jabbour E, Stock W, O'Connell C, Yee K, Tibes R, Griffiths EA, Walsh K, Daver N, Chung W, Naim S, Taverna P, Oganesian A, Hao Y, Lowder JN, Azab M, Kantarjian H. Safety and tolerability of guadecitabine (SGI-110) in patients with myelodysplastic syndrome and acute myeloid leukaemia: a multicentre, randomised, dose-escalation phase 1 study. Lancet Oncol. 2015 Sep;16(9):1099-1110. doi: 10.1016/S1470-2045(15)00038-8. Epub 2015 Aug 19.

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2011
• Primary Completion (Actual): July 22, 2016
• Study Completion (Actual): July 22, 2016

Study Registration Dates

• First Submitted: November 29, 2010
• First Submitted That Met QC Criteria: December 15, 2010
• First Posted (Estimated): December 16, 2010

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 27, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: AML; DNA Hypomethylating Agent; SGI-110; Intermediate 1, Intermediate 2, CMML or High Risk MDS
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Precancerous Conditions; Bone Marrow Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Myelodysplastic Syndromes; Antineoplastic Agents; Guadecitabine
• Other Study ID Numbers: SGI-110-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No