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SGI-110 in Adults With Untreated Acute Myeloid Leukemia (AML), Not Considered Candidates for Intensive Remission Induction

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ClinicalTrials.gov Identifier: NCT02348489
Recruitment Status : Completed
First Posted : January 28, 2015
Results First Posted : January 14, 2021
Last Update Posted : January 14, 2021
Sponsor:
Information provided by (Responsible Party):
Astex Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE January 22, 2015
First Posted Date  ICMJE January 28, 2015
Results First Submitted Date  ICMJE November 11, 2020
Results First Posted Date  ICMJE January 14, 2021
Last Update Posted Date January 14, 2021
Actual Study Start Date  ICMJE March 19, 2015
Actual Primary Completion Date May 31, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 21, 2020)
  • Number of Participants With a Complete Response (CR) [ Time Frame: Up to 38 months (median follow-up of 25.5 months) ]
    Number of participants with a best response of CR assessed based on International Working Group 2003 acute myeloid leukemia (AML) response criteria by a blinded independent pathologist.
  • Overall Survival [ Time Frame: At 676 death events (up to 38 months) ]
    Survival time was defined as the number of days from the day the participant was randomly assigned to study treatment to the date of death, regardless of cause.
Original Primary Outcome Measures  ICMJE
 (submitted: January 22, 2015)
  • Complete response (CR) [ Time Frame: 3 years ]
  • Overall Survival [ Time Frame: 3 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 21, 2020)
  • Number of Participants With Composite CR (CRc) [ Time Frame: Up to 38 months (median follow-up of 25.5 months) ]
    CRc is reported as the number of participants with a best response of CR, complete response with incomplete platelet recovery (CRp), or complete response with incomplete blood count recovery (CRi).
  • Number of Days Alive and Out of the Hospital [ Time Frame: Month 6 ]
    The date of each hospital admission and discharge was collected for each participant for up to 6 months, unless the participant died or withdrew consent prior to that time. Duration of each hospital stay in days was calculated as date of discharge minus date of admission. The Number of Days Alive and Out of the Hospital (NDAOH) was calculated as: NDAOH=180 - total duration of all hospital stays within 180 days from the first treatment - number of death days before Day 180. For subjects who were lost to follow-up within 6 months, the NDAOH was calculated conservatively assuming that the subject would have died the day after the last contact day.
  • Progression-free Survival (PFS) [ Time Frame: Up to 38 months (median follow-up of 25.5 months) ]
    Progression-free survival was defined as the number of days from randomization to the earliest date of investigator's assessment of disease progression, participant receiving an alternative anti-leukemia therapy (including hematopoietic cell transplant), or relapse by peripheral blood (PB) assessment or blinded bone marrow (BM) assessment, whichever occurred first, or death, regardless of cause.
  • Number of Red Blood Cell or Platelet Transfusions [ Time Frame: Month 6 ]
    The total number of red blood cells (RBCs) transfused or, separately, the total number of platelets transfused up to the 6-month time point for each participant was counted from the date of randomization to Day 180, the date of last contact, or date of death, whichever occurred earlier. One RBC or platelet transfusion was defined as one unit, and a single bag of RBCs or platelets was considered one unit.
  • Change in Health-related Quality of Life (QOL) Scores From Baseline: EQ-5D-5L [ Time Frame: Baseline to Month 6 ]
    EuroQol 5-level 5-dimension (EQ-5D-5L) descriptive scores were collected for each participant for a minimum of 6 months, unless the participant died or withdrew consent. Scores within each dimension for EQ-5D (mobility, self-care, usual activity, pain/discomfort, anxiety/depression) were calculated using counts and proportions. Mean change in scores from baseline are summarized in which an index score of 0 represents the worst health state and 1 represents the best health state.
  • Change in Health-related Quality of Life (QOL) Scores From Baseline: EQ-VAS [ Time Frame: Baseline to Month 6 ]
    EuroQol-Visual Analogue Scale (EQ-VAS) descriptive scores were collected for each participant for a minimum of 6 months, unless the participant died or withdrew consent. A vertical 20-cm scale for EQ-VAS was used where the lowest value of 0 was labeled "the worst health you can imagine" and the top value of 100 was labeled "the best health you can imagine." Mean change in scores from baseline are summarized.
  • Duration of CR [ Time Frame: Up to 38 months (median follow-up of 25.5 months) ]
    Duration of CR (in number of days) was calculated from the first time a CR was observed to the time of relapse, defined as the earliest time point whereby BM assessment or PB assessment indicated relapse/disease progression due to reappearance of leukemic blasts in PB or ≥ 5% leukemic blasts in BM.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 22, 2015)
  • Composite CR [ Time Frame: 3 years ]
  • Number of Days Alive and Out of the Hospital [ Time Frame: 3 years ]
  • Progression-free Survival (PFS) [ Time Frame: 3 years ]
  • Number of Red Blood Cell or Platelet Transfusions [ Time Frame: 3 years ]
  • Health-related quality of life (QOL) [ Time Frame: 3 years ]
  • Duration of CR [ Time Frame: 3 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE SGI-110 in Adults With Untreated Acute Myeloid Leukemia (AML), Not Considered Candidates for Intensive Remission Induction
Official Title  ICMJE A Phase 3, Multicenter, Open-label, Randomized Study of SGI-110 Versus Treatment Choice (TC) in Adults With Previously Untreated Acute Myeloid Leukemia (AML) Who Are Not Considered Candidates for Intensive Remission Induction Chemotherapy
Brief Summary To compare efficacy and safety between SGI-110 and Treatment Choice in adults with previously untreated AML who are not considered candidates for intensive remission induction chemotherapy.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Leukemia, Myeloid, Acute
Intervention  ICMJE
  • Drug: SGI-110 (guadecitabine)
    Investigational medicinal product
  • Drug: Treatment Choice
    Choice of one: cytarabine, decitabine, or azacitidine
Study Arms  ICMJE
  • Experimental: SGI-110 (guadecitabine)
    Guadecitabine 60 mg/m^2 administered subcutaneously (SC) daily for 5 days (Days 1-5) in 28-day cycles.
    Intervention: Drug: SGI-110 (guadecitabine)
  • Active Comparator: Treatment Choice
    One of the following treatment regimens: 20 mg cytarabine administered subcutaneously (SC) twice daily (BID) on Days 1-10 every 28 days; 20 mg/m^2 decitabine given as a 1-hour intravenous (IV) infusion daily on Days 1-5 every 28 days; or 75 mg/m^2 azacitidine given IV or SC daily on Days 1-7 every 28 days.
    Intervention: Drug: Treatment Choice
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 4, 2017)
815
Original Estimated Enrollment  ICMJE
 (submitted: January 22, 2015)
800
Actual Study Completion Date  ICMJE June 17, 2019
Actual Primary Completion Date May 31, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Cytologically or histologically confirmed diagnosis of AML (except M3 acute promyelocytic leukemia) according to World Health Organization (WHO) classification.

Performance status (ECOG) of 0-3. Adults with previously untreated AML except for hydroxyurea or corticosteroids. Prior hydroxyurea or lenalidomide treatment for myelodysplastic syndrome (MDS) is allowed.

Not considered candidates for intensive remission induction chemotherapy at time of enrollment based on EITHER:

  1. ≥75 years of age OR
  2. <75 years of age with at least 1 of the following:

i. Poor performance status (ECOG) score of 2-3.

ii. Clinically significant heart or lung comorbidities, as reflected by at least 1 of:

  1. Left ventricular ejection fraction (LVEF) ≤50%.
  2. Lung diffusing capacity for carbon monoxide (DLCO) ≤65% of expected.
  3. Forced expiratory volume in 1 second (FEV1) ≤65% of expected.
  4. Chronic stable angina or congestive heart failure controlled with medication.

iii. Liver transaminases >3 × upper limit of normal (ULN).

iv. Other contraindication(s) to anthracycline therapy (must be documented).

v. Other comorbidity the investigator judges incompatible with intensive remission induction chemotherapy, which must be documented and approved by the study medical monitor before randomization.

Creatinine clearance as estimated by the Cockcroft-Gault (C-G) or other medically acceptable formulas ≥30 mL/min.

Exclusion Criteria:

Candidate for intensive remission induction chemotherapy at the time of enrollment.

Candidate for best supportive care only, ie, not a candidate for any active therapy with the TC comparators.

Known extramedullary central nervous system (CNS) AML.

Second malignancy currently requiring active therapy except breast or prostate cancer stable on or responding to endocrine therapy.

Prior treatment with decitabine or azacitidine.

Hypersensitivity to decitabine, SGI-110, or SGI-110 excipients.

Known active human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection. Inactive hepatitis carrier status or low viral hepatitis titer on antivirals is allowed.

Known significant mental illness or other condition such as active alcohol or other substance abuse or addiction that, in the opinion of the investigator, predisposes the subject to high risk of noncompliance with the protocol.

Refractory congestive heart failure unresponsive to medical treatment; active infection resistant to all antibiotics; or advanced pulmonary disease requiring >2 liters per minute (LPM) oxygen.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   Bulgaria,   Canada,   Czechia,   Denmark,   Finland,   France,   Germany,   Hungary,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Poland,   Romania,   Russian Federation,   Serbia,   Spain,   Sweden,   Taiwan,   United Kingdom,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT02348489
Other Study ID Numbers  ICMJE SGI-110-04
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Astex Pharmaceuticals, Inc.
Study Sponsor  ICMJE Astex Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Astex Pharmaceuticals, Inc.
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP