Clinical Trials /

Guadecitabine (SGI-110) vs Treatment Choice in Adults With MDS or CMML Previously Treated With HMAs

NCT02907359

Description:

A Phase 3, randomized, open-label, parallel-group, multicenter study designed to evaluate the efficacy and safety of guadecitabine in subjects with MDS or CMML who failed or relapsed after adequate prior treatment with azacitidine, decitabine, or both. This global study will be conducted in approximately 15 countries. Approximately 408 subjects from approximately 100 study centers will be randomly assigned in a 2:1 ratio to either guadecitabine (approximately 272 subjects) or Treatment Choice (approximately 136 subjects). The study consists of 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 more than 2 years, and the duration of individual subject participation will vary. Subjects may continue to receive treatment for as long as they continue to benefit.

Related Conditions:
  • Chronic Myelomonocytic Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Guadecitabine (SGI-110) vs Treatment Choice in Adults With MDS or CMML Previously Treated With HMAs
  • Official Title: A Phase 3, Multicenter, Randomized, Open-Label Study of Guadecitabine (SGI-110) Versus Treatment Choice in Adults With Myelodysplastic Syndromes (MDS) or Chronic Myelomonocytic Leukemia (CMML) Previously Treated With Hypomethylating Agents

Clinical Trial IDs

  • ORG STUDY ID: SGI-110-07
  • NCT ID: NCT02907359

Conditions

  • Myelodysplastic Syndromes
  • Leukemia, Myelomonocytic, Chronic

Interventions

DrugSynonymsArms
GuadecitabineSGI-110Guadecitabine

Purpose

A Phase 3, randomized, open-label, parallel-group, multicenter study designed to evaluate the efficacy and safety of guadecitabine in subjects with MDS or CMML who failed or relapsed after adequate prior treatment with azacitidine, decitabine, or both. This global study will be conducted in approximately 15 countries. Approximately 408 subjects from approximately 100 study centers will be randomly assigned in a 2:1 ratio to either guadecitabine (approximately 272 subjects) or Treatment Choice (approximately 136 subjects). The study consists of 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 more than 2 years, and the duration of individual subject participation will vary. Subjects may continue to receive treatment for as long as they continue to benefit.

Detailed Description

      Multicenter, randomized, open-label, parallel-group study of guadecitabine vs Treatment
      Choice (TC). Approximately 408 subjects will be randomly assigned 2:1 to either guadecitabine
      or TC.

        -  Guadecitabine: approximately 272 subjects.

        -  TC: approximately 136 subjects.

      Before randomization, the investigator will assign each subject to one of the following TC
      options:

        -  Low dose cytarabine (LDAC).

        -  Standard Intensive Chemotherapy (IC) of a 7+3 regimen.

        -  Best Supportive Care (BSC) only. BSC will be provided to all subjects as per standard
           and institutional practice. Subjects randomized to TC will not be allowed to cross over
           to guadecitabine. Data will be reviewed by an independent Data Monitoring Committee at
           regular intervals, primarily to evaluate safety during study conduct. Randomization will
           be stratified by disease category (MDS vs CMML), bone marrow (BM) blasts (BM blasts >10%
           vs BM blasts ≤10%), TC option (LDAC vs IC vs BSC), and study center region.

      Guadecitabine: 60 mg/m2 given SC daily on Days 1-5 in 28-day cycles (delayed as needed to
      allow blood count recovery). Treatment should be given for at least 6 total cycles in the
      absence of unacceptable toxicity or disease progression requiring alternative therapy. Beyond
      6 cycles, treatment should continue as long as the subject continues to benefit. BSC should
      be given according to standard and institutional practice.

      Treatment Choice (TC): Before randomization, the investigator will assign each subject to one
      of the following TC options:

        -  Low dose cytarabine (LDAC) given as 20 mg/m2 SC or IV once daily for 14 days in 28-day
           cycles (delayed as needed to allow blood count recovery). Treatment should be given for
           at least 4 cycles in the absence of disease progression or unacceptable toxicity.

        -  Standard Intensive Chemotherapy (IC) of a 7+3 regimen: given as cytarabine 100-200
           mg/m2/day given as continuous infusion for 7 days and an anthracycline given as per
           institutional standard practice such as daunorubicin (45-60 mg/m2/day), or idarubicin
           (9-12 mg/m2/day), or mitoxantrone (8-12 mg/m2/day) by intravenous infusion for 3 days.

        -  Best Supportive Care (BSC) only: given according to standard and institutional practice.
           BSC includes, but is not limited to blood transfusions (RBCs or platelets), growth
           factors including erythropoiesis stimulating agents (ESA), granulocyte stimulating
           factors (GSFs), iron chelating therapy, and broad spectrum antibiotics and/or
           antifungals.
    

Trial Arms

NameTypeDescriptionInterventions
GuadecitabineExperimentalGuadecitabine 60 mg/m2 given subcutaneously daily on Days 1-5 in 28-day cycles. The total amount (in mg) of guadecitabine to be administered is determined by body surface area.
  • Guadecitabine
Treatment ChoiceActive ComparatorBest Supportive Care. Low dose cytarabine. Standard Intensive Chemotherapy.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Adult subjects ≥18 years of age who are able to understand and comply with study
                 procedures, and provide written informed consent before any study-specific procedure.
    
              -  Cytologically or histologically confirmed diagnosis of MDS or CMML according to the
                 2008 World Health Organization (WHO) classification.
    
              -  Performance status (ECOG) of 0-2.
    
              -  Previously treated MDS or CMML, defined as prior treatment with at least one
                 hypomethylating agent (HMA; azacitidine and/or decitabine) for intermediate or high
                 risk MDS or CMML whose disease progressed or relapsed as follows:
    
                   1. Subject received HMA for at least 6 cycles and was still transfusion dependent
                      (as defined in 5b below).
    
                   2. Subject had disease progression prior to Cycle 6 defined as ≥50% increase in bone
                      marrow blasts from pretreatment levels to >5%, or ≥2 g/dL reduction of Hgb from
                      pretreatment levels with transfusion dependence after at least 2 cycles of HMA.
    
            Other prior treatments for MDS such as lenalidomide, cytarabine, intensive chemotherapy,
            hydroxyurea, erythropoietin and other growth factors, or hematopoietic cell transplant
            (HCT) are allowed.
    
              -  Subjects must have either:
    
                   1. Bone marrow blasts >5% at randomization, OR
    
                   2. Transfusion dependence, defined as having had transfusion (in the setting of
                      active disease) of 2 or more units of RBC or platelets within 8 weeks prior to
                      randomization.
    
              -  Creatinine clearance or glomerular filtration rate ≥30 mL/min 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).
    
              -  Women of childbearing potential must not be pregnant or breastfeeding and must have a
                 negative pregnancy test at screening. Women of childbearing potential and men with
                 female partners of childbearing potential must agree to practice 2 highly effective
                 contraceptive measures of birth control and must agree not to become pregnant or
                 father a child while receiving treatment with guadecitabine, LDAC, or IC and for at
                 least 3 months after completing treatment.
    
            Exclusion criteria:
    
              -  Subjects who have been diagnosed as having AML with peripheral blood or bone marrow
                 blasts of ≥20%.
    
              -  Subjects who may still be sensitive to repeated treatment with decitabine or
                 azacitidine such as subjects who had response to prior decitabine or azacitidine
                 treatment, but relapsed >6 months after stopping treatment with these agents.
    
              -  Prior treatment with guadecitabine.
    
              -  Hypersensitivity to decitabine, guadecitabine, or any of their excipients.
    
              -  Second malignancy currently requiring active therapy, except breast or prostate cancer
                 stable on or responding to endocrine therapy.
    
              -  Treated with any investigational drug within 2 weeks of the first dose of study
                 treatment.
    
              -  Total serum bilirubin >2.5 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.
    
              -  Known active HIV, HBV, or 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 non-MDS associated pulmonary
                 disease requiring >2 liters per minute oxygen.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Overall survival
    Time Frame:18 Months
    Safety Issue:
    Description:

    Secondary Outcome Measures

    Measure:Transfusion independence
    Time Frame:18 months
    Safety Issue:
    Description:
    Measure:Marrow complete response
    Time Frame:18 months
    Safety Issue:
    Description:
    Measure:Survival rate
    Time Frame:18 months
    Safety Issue:
    Description:
    Measure:Leukemia-free survival
    Time Frame:18 months
    Safety Issue:
    Description:As described in Time Frame.
    Measure:Number of days alive and out of the hospital (NDAOH).
    Time Frame:18 months
    Safety Issue:
    Description:
    Measure:Disease response
    Time Frame:18 months
    Safety Issue:
    Description:
    Measure:Duration of response
    Time Frame:18 months
    Safety Issue:
    Description:
    Measure:Number of transfusions
    Time Frame:18 months
    Safety Issue:
    Description:
    Measure:Health-related quality of life
    Time Frame:18 months
    Safety Issue:
    Description:
    Measure:Incidence and severity of adverse events.
    Time Frame:18 months
    Safety Issue:
    Description:
    Measure:30-day and 60-day all-cause mortality
    Time Frame:18 months
    Safety Issue:
    Description:

    Details

    Phase:Phase 3
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Astex Pharmaceuticals

    Last Updated