Clinical Trials /

Phase 3 Randomized, Open-Label Study of Guadecitabine vs Treatment Choice in Previously Treated Acute Myeloid Leukemia

NCT02920008

Description:

Multicenter, randomized, open-label, parallel-group study of guadecitabine vs treatment choice (TC). Subjects will be randomly assigned in a 1:1 ratio to either guadecitabine or TC. TC options include the 8 high or low intensity, locally available regimens below; or Best supportive Care (BSC) alone: - High intensity (intermediate or high dose cytarabine [HiDAC]; mitoxantrone, etoposide, and cytarabine [MEC]; or fludarabine, cytarabine, granulocyte colony stimulating factor [G-CSF], +/- idarubicin [FLAG/FLAG-Ida]). - Low intensity (low dose cytarabine [LDAC], decitabine, or azacitidine). - BSC.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Phase 3 Randomized, Open-Label Study of Guadecitabine vs Treatment Choice in Previously Treated Acute Myeloid Leukemia
  • Official Title: A Phase 3, Multicenter, Randomized, Open-Label Study of Guadecitabine (SGI-110) Versus Treatment Choice in Adults With Previously Treated Acute Myeloid Leukemia

Clinical Trial IDs

  • ORG STUDY ID: SGI-110-06
  • NCT ID: NCT02920008

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
guadecitabineSGI-110guadecitabine
Treatment Choice (TC)Treatment Choice (TC)

Purpose

Multicenter, randomized, open-label, parallel-group study of guadecitabine vs treatment choice (TC). Subjects will be randomly assigned in a 1:1 ratio to either guadecitabine or TC. TC options include the 8 high or low intensity, locally available regimens below; or Best supportive Care (BSC) alone: - High intensity (intermediate or high dose cytarabine [HiDAC]; mitoxantrone, etoposide, and cytarabine [MEC]; or fludarabine, cytarabine, granulocyte colony stimulating factor [G-CSF], +/- idarubicin [FLAG/FLAG-Ida]). - Low intensity (low dose cytarabine [LDAC], decitabine, or azacitidine). - BSC.

Detailed Description

      This Phase 3, randomized, open-label, parallel-group multicenter study of the efficacy and
      safety of guadecitabine in adults with previously treated AML will be conducted in
      approximately 20 countries. There will be a 14-day screening period, a treatment period, a
      safety follow-up visit, and a long-term follow-up period. The study is expected to last
      approximately 2 years. Duration of individual subject participation will vary, and subjects
      may continue to receive treatment for as long as they continue to benefit.

      Approximately 404 subjects from approximately 100 study centers will be randomly assigned to
      either guadecitabine or treatment choice (TC) in a 1:1 ratio (approximately 202 subjects per
      group). TC is as follows:

        -  High intensity: intermediate or high dose cytarabine (HiDAC); mitoxantrone, etoposide,
           and cytarabine (MEC); or fludarabine, cytarabine, G-CSF, +/- idarubicin (FLAG/FLAG-Ida).

        -  Low intensity: low dose cytarabine (LDAC), decitabine, or azacitidine.

        -  Best Supportive Care (BSC).

      Guadecitabine will be given SC at a dose of 60 mg/m2 in 28-day cycles. In Cycle 1,
      guadecitabine will be given for 10 days on Days 1-5 and Days 8-12. Cycle 2 will be either the
      5-day regimen (Days 1-5) or 10-day regimen (Days 1-5 and 8-12) based on assessment of disease
      response and hematologic recovery at the end of Cycle 1. In subsequent cycles, guadecitabine
      treatment will be for 5 days only (Days 1-5).
    

Trial Arms

NameTypeDescriptionInterventions
guadecitabineExperimentalGuadecitabine will be given SC at a dose of 60 mg/m2 in 28-day cycles (delayed as necessary to allow blood count recovery).
  • guadecitabine
Treatment Choice (TC)Active ComparatorHigh intensity Low intensity Best supportive care (BSC).
  • Treatment Choice (TC)

Eligibility Criteria

        Inclusion Criteria:

          1. Adult subjects ≥18 years of age who are able to understand study procedures, comply
             with them, and provide written informed consent before any study-specific procedure.

          2. History of cytologically or histologically confirmed diagnosis of AML (except acute
             promyelocytic leukemia) according to the 2008 World Health Organization (WHO)
             classification (bone marrow [BM] or peripheral blood [PB] blast counts ≥20%).

          3. Performance status (Eastern Cooperative Oncology Group; ECOG) of 0-2.

          4. Subjects with AML previously treated with initial induction therapy using a standard
             intensive chemotherapy regimen, including cytarabine and an anthracycline, and who are
             refractory to initial induction (primary refractory) or in relapse after such initial
             induction with or without prior HCT.

          5. Subjects must have either PB or BM blasts ≥5% at time of randomization.

          6. Creatinine clearance or glomerular filtration rate ≥30 mL/min as estimated by the
             Cockroft-Gault (C-G) or other medically acceptable formulas, such as MDRD
             (Modification of Diet in Renal Disease) or CKD-EPI (the Chronic Kidney Disease
             Epidemiology Collaboration).

          7. Women of child-bearing potential must not be pregnant or breastfeeding and must have a
             negative pregnancy test at screening. Women of child-bearing potential and men with
             female partners of child-bearing potential must agree to practice 2 highly effective
             contraceptive measures of birth control and must agree not to become pregnant or
             father a child (a) while receiving treatment of guadecitabine, decitabine, or
             azacitidine and for at least 3 months after completing treatment and (b) while
             receiving treatment with high-intensity TC or LDAC and for at least 6 months after
             completing treatment.

        Exclusion Criteria:

          1. Known clinically active central nervous system (CNS) or extramedullary AML, except
             leukemia cutis.

          2. Subjects who are in first relapse after initial induction, if they had a response
             duration of >12 months from date when first response first documented or if they are
             good candidates for HCT.

          3. BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis).

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

          5. Grade 3 or higher Graft Versus Host Disease (GVHD), or GVHD on either a calcineurin
             inhibitor or prednisone more than 5 mg/day.

          6. Prior treatment with guadecitabine for any indication, or more than 2 cycles of prior
             decitabine or azacitidine.

          7. Hypersensitivity to decitabine, guadecitabine, or any of their excipients.

          8. Treated with any investigational therapy within 2 weeks of the first dose of study
             treatment.

          9. Total serum bilirubin >2.5 × upper limit of normal (ULN; except for subjects with
             Gilbert's Syndrome for whom direct bilirubin is <2.5 × ULN), or liver cirrhosis, or
             chronic liver disease Child-Pugh Class B or C.

         10. 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.

         11. 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.

         12. Refractory congestive heart failure unresponsive to medical treatment; active
             infection resistant to all antibiotics; or non-AML-associated pulmonary disease
             requiring >2 liters per minute (LPM) oxygen, or any other condition that puts the
             subject at an imminent risk of death.

         13. Subjects with high PB blasts >50% AND poor ECOG PS of 2.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall survival
Time Frame:24 months
Safety Issue:
Description:Number of days from day subject was randomized to date of death, regardless of cause.

Secondary Outcome Measures

Measure:Event-free survival
Time Frame:24 months
Safety Issue:
Description:Number of days from randomization to earliest date of disease progression, treatment discontinuation, start of anti-leukemia therapy, or death.
Measure:Long-term survival
Time Frame:24 months
Safety Issue:
Description:Survival at one year.
Measure:Number of days alive and out of the hospital (NDAOH).
Time Frame:24 months
Safety Issue:
Description:Number of days subject alive and out of hospital during first 6 months of the study.
Measure:Transfusion independence rate
Time Frame:24 months
Safety Issue:
Description:Number of subjects without RBC or platelet transfusion for any 8-week period after treatment divided by total number of subjects in efficacy analysis.
Measure:Complete response rate
Time Frame:24 months
Safety Issue:
Description:Number of subjects with best response of CR divided by total number of subjects in efficacy analysis.
Measure:Composite complete response
Time Frame:24 months
Safety Issue:
Description:Number of subjects with best response of CR, CRp, or CRi divided by total number of subjects in efficacy analysis.
Measure:Hematopoietic cell transplant (HCT) rate
Time Frame:24 months
Safety Issue:
Description:Number of subjects who received HCT after randomization divided by total number of subjects in efficacy analysis.
Measure:Duration of complete response (CR)
Time Frame:24 months
Safety Issue:
Description:Duration of CR (in number of days) will be calculated from the first time a CR is observed to time of relapse (defined as the earliest time point whereby BM assessment or PB assessment indicate relapse/disease progression due to confirmed reappearance of ≥5% leukemic blasts in PB or ≥5% leukemic blasts in BM.
Measure:Quality of life
Time Frame:6 months
Safety Issue:
Description:The calculation for EQ-5D-5L index value will be performed according to EuroQol group's EQ-5D-5L User Guide.
Measure:Incidence and severity of adverse events
Time Frame:24 months
Safety Issue:
Description:Subject reported and investigator-observed AEs and 30- and 60-day all-cause mortality, along with clinical laboratory tests (hematology, chemistries), concomitant Medications, physical examination, vital signs, ECOG performance status and ECGs.
Measure:30- and 60-day all-cause mortality
Time Frame:24 months
Safety Issue:
Description:Number of deaths, regardless of cause, within 30 or 60 days from the first study dose divided by the total number of subjects included in the safety analysis set.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Astex Pharmaceuticals

Trial Keywords

  • AML, acute myeloid leukemia, guadecitabine, SGI-110, Phase 3

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