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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/Phase 2
18 Years
N/A
Open (Enrolling)
Both
MDS, CMML, AML

Thank you

Trial Information

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)


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.


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.

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label

Outcome Measure:

Dose Escalation Segment (Safety Lead-in): Determine the optimal BED or MTD and the frequency of drug administration.

Outcome Description:

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

Outcome Time Frame:

Assessed at the end of Course 1 (4 weeks) for each dose cohort.

Safety Issue:

Yes

Authority:

United States: Food and Drug Administration

Study ID:

SGI-110-01

NCT ID:

NCT01261312

Start Date:

December 2010

Completion Date:

December 2013

Related Keywords:

  • MDS
  • CMML
  • AML
  • SGI-110
  • DNA Hypomethylating Agent
  • Intermediate 1, Intermediate 2, CMML or High Risk MDS
  • AML
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Myelodysplastic Syndromes
  • Preleukemia

Name

Location

MD Anderson Cancer Center Houston, Texas  77030-4096
Roswell Park Cancer Institute Buffalo, New York  14263
Temple University Philadelphia, Pennsylvania  19140
Duke University Durham, North Carolina  27710
Ohio State University Columbus, Ohio  43210
Mayo Clinic Scottsdale, Arizona  
University of Southern California Los Angeles, California  90033
Cornell University New York, New York  10021
Tennessee Oncology Nashville, Tennessee  37203
University of Chicago Cancer Center Chicago, Illinois  60637