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

NCT ID: NCT01261312

Last Updated: 2025-01-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 414 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-04
• Study Completion Date: 2016-07-22

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.

Conditions

MDS; CMML; AML

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Guadecitabine

Intervention Type: DRUG

Subcutaneous injection

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.

Group Type: EXPERIMENTAL

Guadecitabine

Intervention Type: DRUG

Subcutaneous injection

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.

Group Type: EXPERIMENTAL

Guadecitabine

Intervention Type: DRUG

Subcutaneous injection

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.

Group Type: EXPERIMENTAL

Guadecitabine

Intervention Type: DRUG

Subcutaneous injection

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.

Group Type: EXPERIMENTAL

Guadecitabine

Intervention Type: DRUG

Subcutaneous injection

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.

Group Type: EXPERIMENTAL

Guadecitabine

Intervention Type: DRUG

Subcutaneous injection

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.

Group Type: EXPERIMENTAL

Guadecitabine

Intervention Type: DRUG

Subcutaneous injection

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.

Group Type: EXPERIMENTAL

Guadecitabine

Intervention Type: DRUG

Subcutaneous injection

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.

Group Type: EXPERIMENTAL

Guadecitabine

Intervention Type: DRUG

Subcutaneous injection

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).

Group Type: EXPERIMENTAL

Guadecitabine

Intervention Type: DRUG

Subcutaneous injection

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.

Group Type: EXPERIMENTAL

Guadecitabine

Intervention Type: DRUG

Subcutaneous injection

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.

Group Type: EXPERIMENTAL

Guadecitabine

Intervention Type: DRUG

Subcutaneous injection

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.

Group Type: EXPERIMENTAL

Guadecitabine

Intervention Type: DRUG

Subcutaneous injection

Interventions

Guadecitabine

Subcutaneous injection

Intervention Type: DRUG

Other Intervention Names

SGI-110

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Astex Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Mayo Clinic

Scottsdale, Arizona, United States

University of Southern California

Los Angeles, California, United States

Yale University

New Haven, Connecticut, United States

Florida Cancer Specialists - South

Fort Myers, Florida, United States

Florida Cancer Specialists - North

St. Petersburg, Florida, United States

University of Chicago Cancer Center

Chicago, Illinois, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Cornell University

New York, New York, United States

Columbia University Medical Center

New York, New York, United States

Duke University

Durham, North Carolina, United States

Ohio State University

Columbus, Ohio, United States

Temple University

Philadelphia, Pennsylvania, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Tennessee Oncology

Nashville, Tennessee, United States

MD Anderson Cancer Center

Houston, Texas, United States

Princess Margaret Hospital

Toronto, Ontario, Canada

Countries

United States; Canada

References

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.

Reference Type: DERIVED

PMID: 31331399 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31060979 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26296954 (View on PubMed)

Other Identifiers

SGI-110-01

Identifier Type: -

Identifier Source: org_study_id