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

This study is currently recruiting participants.
Verified September 2017 by Daiichi Sankyo, Inc.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02668653
First Posted: January 29, 2016
Last Update Posted: September 29, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.
  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.

Condition Intervention Phase
Acute Myeloid Leukemia Leukemia Drug: Chemotherapy Drug: Quizartinib Drug: Placebo Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Daiichi Sankyo, Inc.:

Primary Outcome Measures:
  • Event-free Survival (EFS) [ Time Frame: Duration of study, an average of 2 years ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: Duration of study, an average 2 years ]
  • Complete remission (CR) rate at the end of the first Induction cycle [ Time Frame: Approximately 42 days ]
  • Composite CR rate at the end of the first Induction cycle [ Time Frame: Approximately 42 days ]
  • Percentage of participants achieving CR with no evidence of minimal residual disease [ Time Frame: Approximately 42 days ]

Estimated Enrollment: 536
Actual Study Start Date: September 2016
Estimated Study Completion Date: November 2020
Estimated Primary Completion Date: November 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Chemotherapy plus quizartinib

Induction: 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

Drug: Chemotherapy
Other Names:
  • Cytarabine
  • Daunorubicin
  • Idarubicin
Drug: Quizartinib
Other Name: Test Product
Active Comparator: Chemotherapy plus placebo

Induction: 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

Drug: Chemotherapy
Other Names:
  • Cytarabine
  • Daunorubicin
  • Idarubicin
Drug: Placebo
Other Name: Placebo Control

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02668653


  Show 199 Study Locations
Sponsors and Collaborators
Daiichi Sankyo, Inc.
Investigators
Study Director: Global Clinical Leader Daiichi Sankyo, Inc.
  More Information

Responsible Party: Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT02668653     History of Changes
Other Study ID Numbers: AC220-A-U302
2015-004856-24 ( EudraCT Number )
First Submitted: January 22, 2016
First Posted: January 29, 2016
Last Update Posted: September 29, 2017
Last Verified: September 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Daiichi Sankyo, Inc.:
Quizartinib
Newly diagnosed Acute Myeloid Leukemia
FLT3-ITD positive
Chemotherapy
Induction chemotherapy
Consolidation chemotherapy
Maintenance chemotherapy
Receptor tyrosine kinase inhibitor
Feline McDonough sarcoma (FMS)-like tyrosine kinase 3
AC220
FLT3-ITD
AML

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Daunorubicin
Idarubicin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors