Clinical Trials /

Quizartinib With Standard of Care Chemotherapy and as Continuation Therapy in Patients With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia (AML)

NCT02668653

Description:

Quizartinib is an experimental drug. It is not approved for regular use. It can only be used in medical research. Adults might be able to join this study after bone marrow tests show they have a certain kind of blood cancer (FLT3-ITD AML). Participants will have an equal chance of receiving quizartinib or placebo along with their chemotherapy.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Quizartinib With Standard of Care Chemotherapy and as Maintenance Therapy in Patients With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia (AML)
  • Official Title: A Phase 3, Double-Blind, Placebo-controlled Study of Quizartinib Administered in Combination With Induction and Consolidation Chemotherapy, and Administered as Maintenance Therapy in Subjects 18 to 75 Years Old With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia

Clinical Trial IDs

  • ORG STUDY ID: AC220-A-U302
  • SECONDARY ID: 2015-004856-24
  • NCT ID: NCT02668653

Conditions

  • Acute Myeloid Leukemia
  • Leukemia

Interventions

DrugSynonymsArms
ChemotherapyCytarabine, Daunorubicin, IdarubicinChemotherapy plus quizartinib
QuizartinibTest ProductChemotherapy plus quizartinib
PlaceboPlacebo ControlChemotherapy plus placebo

Purpose

This is a phase 3, randomized, double-blind, placebo-control global study. The purpose of this study is to compare the effect of quizartinib versus placebo (administered with standard induction and consolidation chemotherapy, then administered as maintenance therapy for up to 12 cycles) on event-free survival in subjects with FLT3-internal tandem duplication (ITD) positive AML.

Trial Arms

NameTypeDescriptionInterventions
Chemotherapy plus quizartinibExperimentalInduction: up to 2 cycles with cytarabine and daunorubicin/idarubicin, followed by the experimental drug quizartinib Consolidation: up to 4 cycles of cytarabine followed by the experimental drug quizartinib and/or hematopoeitic stem cell transplant Maintenance: up to 12 cycles with the experimental drug quizartinib
  • Chemotherapy
  • Quizartinib
Chemotherapy plus placeboActive ComparatorInduction: up to 2 cycles with cytarabine and daunorubicin/idarubicin, followed by placebo Consolidation: up to 4 cycles of cytarabine followed by placebo and/or hematopoeitic stem cell transplant Maintenance: up to 12 cycles with placebo
  • Chemotherapy
  • Placebo

Eligibility Criteria

        Inclusion Criteria:

          1. Must be competent and able to comprehend, sign, and date an Ethics Committee (EC) or
             Institutional Review Board approved Informed Consent Form (ICF) before performance of
             any study-specific procedures or tests;

          2. Is ≥18 years or the minimum legal adult age (whichever is greater) and ≤75 years (at
             Screening);

          3. Newly diagnosed, morphologically documented primary AML or AML secondary to
             myelodysplastic syndrome or a myeloproliferative neoplasm, based on the World Health
             Organization (WHO) 2008 classification (at Screening);

          4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (at the time the
             subject signs their first informed consent form);

          5. Presence of FLT3-ITD activating mutation in bone marrow (allelic ratio of ≥3%
             FLT3-ITD/total FLT3);

          6. Participant is receiving standard "7+3" induction chemotherapy regimen as specified in
             the protocol;

          7. Adequate renal function defined as:

             a. Creatinine clearance >50 mL/min, as calculated with the modified Cockcroft Gault
             equation

          8. Adequate hepatic function defined as:

               1. Total serum bilirubin (TBL) ≤1.5 × upper limit of normal (ULN);

               2. Serum alkaline phosphatase, aspartate transaminase (AST) and alanine transaminase
                  (ALT) ≤2.5 × ULN;

          9. Serum electrolytes within normal limits: potassium, calcium (total, or corrected for
             serum albumin in case of hypoalbuminemia) and magnesium. If outside of normal limits,
             subject will be eligible when electrolytes are corrected;

         10. If a woman of childbearing potential, must have a negative serum pregnancy test upon
             entry into this study and must be willing to use highly effective birth control upon
             enrollment, during the treatment period and for 6 months following the last dose of
             investigational drug or cytarabine, whichever is later. A woman is considered of
             childbearing potential following menarche and until becoming postmenopausal (no
             menstrual period for a minimum of 12 months);

         11. If male, must be surgically sterile or willing to use highly effective birth control
             upon enrollment, during the treatment period, and for 6 months following the last dose
             of investigational drug or cytarabine, whichever is later.

        Exclusion Criteria:

          1. Diagnosis of acute promyelocytic leukemia (APL), French-American-British
             classification M3 or WHO classification of APL with translocation, t(15;17)(q22;q12),
             or breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1
             (BCR-ABL) positive leukemia (ie, chronic myelogenous leukemia in blast crisis);
             subjects who undergo diagnostic workup for APL and treatment with all-trans retinoic
             acid (ATRA), but who are found not to have APL, are eligible (treatment with ATRA must
             be discontinued before starting induction chemotherapy).

          2. Diagnosis of AML secondary to prior chemotherapy or radiotherapy for other neoplasms;

          3. Prior treatment for AML, except for the following allowances:

               -  Leukapheresis;

               -  Treatment for hyperleukocytosis with hydroxyurea;

               -  Cranial radiotherapy for central nervous system (CNS) leukostasis;

               -  Prophylactic intrathecal chemotherapy;

               -  Growth factor/cytokine support;

          4. Prior treatment with quizartinib or other FLT3-ITD inhibitors;

          5. Prior treatment with any investigational drug or device within 30 days prior to
             Randomization (within 2 weeks for investigational or approved immunotherapy) or
             currently participating in other investigational procedures;

          6. History of known CNS leukemia, including cerebrospinal fluid positive for AML blasts;
             lumbar puncture is recommended for subjects with symptoms of CNS leukemia to rule out
             extramedullary CNS involvement;

          7. History of other malignancies, except adequately treated non-melanoma skin cancer,
             curatively treated in-situ disease, or other solid tumors curatively treated with no
             evidence of disease for at least 2 years;

          8. Uncontrolled or significant cardiovascular disease, including any of the following:

               -  Bradycardia of less than 50 beats per minute, unless the subject has a pacemaker;

               -  Fridericia's Heart Rate Correction Formula (QTcF) interval >450 msec;

               -  Diagnosis of or suspicion of long QT syndrome (including family history of long
                  QT syndrome);

               -  Systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg;

               -  History of clinically relevant ventricular arrhythmias (eg, ventricular
                  tachycardia, ventricular fibrillation, or Torsade de Pointes);

               -  History of second (Mobitz II) or third degree heart block (subjects with
                  pacemakers are eligible if they have no history of fainting or clinically
                  relevant arrhythmias while using the pacemaker);

               -  History of uncontrolled angina pectoris or myocardial infarction within 6 months
                  prior to Screening;

               -  History of New York Heart Association Class 3 or 4 heart failure;

               -  Known history of left ventricular ejection fraction (LVEF) ≤45% or less than the
                  institutional lower limit of normal;

               -  Complete left bundle branch block;

          9. Active acute or chronic systemic fungal, bacterial, or viral infection not well
             controlled by antifungal, antibacterial or antiviral therapy;

         10. Known active clinically relevant liver disease (eg, active hepatitis B, or active
             hepatitis C);

         11. Known history of human immunodeficiency virus (HIV). Subjects should be tested for HIV
             prior to Randomization if required by local regulations or EC;

         12. History of hypersensitivity to any excipients in the quizartinib/placebo tablets;

         13. Females who are pregnant or breastfeeding;

         14. Otherwise considered inappropriate for the study by the Investigator.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Event-free Survival (EFS)
Time Frame:Duration of study, an average of 2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall survival
Time Frame:Duration of study, an average 2 years
Safety Issue:
Description:
Measure:Complete remission (CR) rate at the end of the first Induction cycle
Time Frame:Approximately 42 days
Safety Issue:
Description:
Measure:Composite CR rate at the end of the first Induction cycle
Time Frame:Approximately 42 days
Safety Issue:
Description:
Measure:Percentage of participants achieving CR with no evidence of minimal residual disease
Time Frame:Approximately 42 days
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Daiichi Sankyo, Inc.

Trial Keywords

  • Newly diagnosed Acute Myeloid Leukemia
  • FLT3-ITD positive
  • Chemotherapy
  • Induction chemotherapy
  • Consolidation chemotherapy
  • Maintenance chemotherapy
  • Quizartinib
  • Receptor tyrosine kinase inhibitor
  • Feline McDonough sarcoma (FMS)-like tyrosine kinase 3
  • AC220
  • FLT3-ITD
  • AML

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