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

AML Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01261312
• Other study ID #: SGI-110-01
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: December 2010
• Est. completion date: January 2019

Study information

• Verified date: April 2021
• Source: Astex Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 401
• Est. completion date: January 2019
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

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, 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.

Related Conditions & MeSH terms

• AML
• CMML
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• MDS
• Myelodysplastic Syndromes
• Preleukemia

Intervention

Drug:
• SGI-110
SGI-110 subcutaneous injection administered on Days 1-5 SGI-110 subcutaneous injection administered on Days 1-5 and 8-12
• 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

Locations

Country	Name	City	State
Canada	Princess Margaret Hospital	Toronto	Ontario
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	University of Chicago Cancer Center	Chicago	Illinois
United States	Ohio State University	Columbus	Ohio
United States	Duke University	Durham	North Carolina
United States	Florida Cancer Specialists - South	Fort Myers	Florida
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of Southern California	Los Angeles	California
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Tennessee Oncology	Nashville	Tennessee
United States	Yale University	New Haven	Connecticut
United States	Columbia University Medical Center	New York	New York
United States	Cornell University	New York	New York
United States	Temple University	Philadelphia	Pennsylvania
United States	Florida Cancer Specialists - North	Saint Petersburg	Florida
United States	Mayo Clinic	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Astex Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Escalation Segment (Safety Lead-in): Determine the optimal BED or MTD and the frequency of drug administration.	Number of patients with adverse events.; Incidence of dose limiting toxicities.; Degree of hypomethylation as measured by LINE-1.	Assessed at the end of Course 1 (4 weeks) for each dose cohort.
Primary	Dose Expansion Segment: Assess the activity of SGI-110 as measured by overall remission rate.	Overall survival measured in weeks.	12 Months
Secondary	Determine the pharmacokinetic profile of SGI-110 and decitabine.	Cmax, Cmin, AUC and other secondary PK parameters of SGI-110 and decitabine in patients during Course 1.	Assessed at the end of Course 1 (4 weeks) for each cohort.
Secondary	Remission duration, hematological improvements and transfusion independence rates.	Assess remission duration, hematological improvement and transfusion independence rates as measured by weeks.	12 months
Secondary	Determine epigenetic modulation in peripheral blood and bone marrow samples.		12 months