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

• Sponsor: Astex Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01261312
• Collaborator: (none)
• Enrollment: 401
• Locations: 16
• Arms: 2
• Duration (Months): 97
• Patients Per Site: 25.1
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

Phase 1-2 dose escalation randomized study in patients 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 patients 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.

Condition or Disease	Intervention/Treatment	Phase
MDS; CMML; AML	Drug: SGI-110; Drug: SGI-110	Phase 1/Phase 2

Detailed Description

Once the BED and MTD is determined in the Dose Escalation Segment, the Dose Expansion Segment will randomize patients with MDS, treatment naïve elderly AML, and relapsed/refractory AML patients to receive the BED or MTD dose. Relapsed/refractory AML patients 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 Design

• Study Type: Interventional
• Actual Enrollment: 401 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: 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)
• Study Start Date: Dec 1, 2010
• Actual Primary Completion Date: Jul 1, 2016
• Actual Study Completion Date: Jan 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Daily Regimen SGI-110 daily x5 dosing on a 28-day course SGI-110 daily x10 dosing on a 28-day course	Drug: SGI-110; SGI-110 subcutaneous injection administered on Days 1-5 SGI-110 subcutaneous injection administered on Days 1-5 and 8-12
Experimental: Weekly Regimen SGI-110 weekly dosing for three weeks on a 28-day course SGI-110 twice weekly dosing for three weeks on a 28-day course	Drug: SGI-110; SGI-110 administered weekly on Days 1, 8 and 15 SGI-110 administered weekly on Days 1, 4, 8, 11, 15, and 18

Outcome Measures

Primary Outcome Measures

1. Dose Escalation Segment (Safety Lead-in): Determine the optimal BED or MTD and the frequency of drug administration. [Assessed at the end of Course 1 (4 weeks) for each dose cohort.]

   Number of patients with adverse events. Incidence of dose limiting toxicities. Degree of hypomethylation as measured by LINE-1.

2. Dose Expansion Segment: Assess the activity of SGI-110 as measured by overall remission rate. [12 Months]

   Overall survival measured in weeks.

Secondary Outcome Measures

1. Determine the pharmacokinetic profile of SGI-110 and decitabine. [Assessed at the end of Course 1 (4 weeks) for each cohort.]

   Cmax, Cmin, AUC and other secondary PK parameters of SGI-110 and decitabine in patients during Course 1.

2. Remission duration, hematological improvements and transfusion independence rates. [12 months]

   Assess remission duration, hematological improvement and transfusion independence rates as measured by weeks.

3. Determine epigenetic modulation in peripheral blood and bone marrow samples. [12 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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, patients who are refractory, relapsed, or unresponsive to standard treatment.

• In the Dose Expansion Segment, hypomethylating agent (HMA) treatment-naïve MDS subjects (including CMML), and intermediate-2 or high-risk MDS subjects (including CMML) relapsed or refractory to prior HMA treatment are allowed, and treatment-naïve AML subjects who are 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

1. Eastern ECOG performance status of 0 to 2.

2. Adequate organ function.

3. Prior allogeneic stem cell transplant, no evidence of active graft-versus host disease (GVHD) and must be ≥ 2 weeks off immunosuppressive therapy.

4. No major surgery within 4 weeks of first dose of SGI-110.

5. 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.

6. Sign an approved informed consent form for this study.

Exclusion Criteria:

1. In the Dose Expansion Segment, which includes the 10-day regimen, subjects 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 subjects (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 patient 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 patient'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 patients, patients 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Scottsdale	Arizona	United States	85259
2	University of Southern California	Los Angeles	California	United States	90033
3	Yale University	New Haven	Connecticut	United States	06520
4	Florida Cancer Specialists - South	Fort Myers	Florida	United States	33916
5	Florida Cancer Specialists - North	Saint Petersburg	Florida	United States	33705
6	University of Chicago Cancer Center	Chicago	Illinois	United States	60637
7	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
8	Cornell University	New York	New York	United States	10021
9	Columbia University Medical Center	New York	New York	United States	10032
10	Duke University	Durham	North Carolina	United States	27705
11	Ohio State University	Columbus	Ohio	United States	43210
12	Temple University	Philadelphia	Pennsylvania	United States	19111
13	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
14	Tennessee Oncology	Nashville	Tennessee	United States	37203
15	MD Anderson Cancer Center	Houston	Texas	United States	77030
16	Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9

Sponsors and Collaborators

• Astex Pharmaceuticals, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Astex Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT01261312
• Other Study ID Numbers: SGI-110-01
• First Posted: Dec 16, 2010
• Last Update Posted: Apr 20, 2021
• Last Verified: Apr 1, 2021

• Keywords provided by Astex Pharmaceuticals, Inc.: SGI-110; DNA Hypomethylating Agent; Intermediate 1, Intermediate 2, CMML or High Risk MDS; AML
• Additional relevant MeSH terms: Preleukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Guadecitabine; Azacitidine

Study Results

No Results Posted as of Apr 20, 2021