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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Astex Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01261312
First received: November 29, 2010
Last updated: September 24, 2014
Last verified: September 2014
  Purpose

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 Intervention Phase
MDS
CMML
AML
Drug: SGI-110
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
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)

Resource links provided by NLM:


Further study details as provided by Astex Pharmaceuticals:

Primary Outcome Measures:
  • Dose Escalation Segment (Safety Lead-in): Determine the optimal BED or MTD and the frequency of drug administration. [ Time Frame: Assessed at the end of Course 1 (4 weeks) for each dose cohort. ] [ Designated as safety issue: Yes ]
    • Number of patients with adverse events.
    • Incidence of dose limiting toxicities.
    • Degree of hypomethylation as measured by LINE-1.

  • Dose Expansion Segment: Assess the activity of SGI-110 as measured by overall remission rate. [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
    Overall survival measured in weeks.


Secondary Outcome Measures:
  • Determine the pharmacokinetic profile of SGI-110 and decitabine. [ Time Frame: Assessed at the end of Course 1 (4 weeks) for each cohort. ] [ Designated as safety issue: No ]
    Cmax, Cmin, AUC and other secondary PK parameters of SGI-110 and decitabine in patients during Course 1.

  • Remission duration, hematological improvements and transfusion independence rates. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Assess remission duration, hematological improvement and transfusion independence rates as measured by weeks.

  • Determine epigenetic modulation in peripheral blood and bone marrow samples. [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 300
Study Start Date: December 2010
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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, 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01261312

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

No publications provided

Responsible Party: Astex Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01261312     History of Changes
Other Study ID Numbers: SGI-110-01
Study First Received: November 29, 2010
Last Updated: September 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Astex Pharmaceuticals:
SGI-110
DNA Hypomethylating Agent
Intermediate 1, Intermediate 2, CMML or High Risk MDS
AML

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Leukemia
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on October 19, 2014