Protocol Summary

Protocol No.: OCR14956

Sponsor Protocol No.: AC220-A-U302

Study Title
A Phase 3, Double-Blind, Placebo-Controlled Study of Quizartinib (AC220) 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

Principal Investigator(s)
Hsu, Jack

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-ITD positive AML.

Phase: Phase III

Age Group: Adult

Scope: National

Experimental: Induction and consolidation chemotherapy plus quizartinib
A. Induction: up to 2 cycles with cytarabine and daunorubicin/idarubicin, followed by the experimental drug quizartinib
B. Consolidation: up to 4 cycles of cytarabine followed by the experimental drug quizartinib and/or hematopoeitic stem cell transplant
C. Maintenance: up to 12 cycles with the experimental drug quizartinib

Active Comparator: Induction and consolidation chemotherapy plus placebo
A. Induction: up to 2 cycles with cytarabine and daunorubicin/idarubicin, followed by placebo
B. Consolidation: up to 4 cycles of cytarabine followed by placebo and/or hematopoeitic stem cell transplant
C. Maintenance: up to 12 cycles with placebo

Detailed Eligibility
1. Ages 18 to 75 years old
2. 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;
3. Newly diagnosed, morphologically documented primary AML or AML secondary to myelodysplastic syndrome, based on the World Health Organization (WHO) 2008 classification (at Screening);
4. Eastern Cooperative Oncology Group performance status 0-2 (at Screening);
5. Presence of FLT3-ITD activating mutation in bone marrow (allelic ratio of ≥3% FLT3-ITD/total FLT3);
6. Subject is receiving standard "7+3" induction chemotherapy regimen as specified in the protocol;
7. Adequate renal function defined as:
- Serum creatinine ≤1.5 × the upper limit of normal (ULN); or
- Glomerular filtration rate >50 mL/min/1.73m2, as calculated with the modified Cockcroft Gault equation;
8. Adequate hepatic function defined as:
- Total serum bilirubin ≤1.5 × ULN;
- Serum alkaline phosphatase, aspartate transaminase and alanine transaminase ≤2.5 × ULN;
9. Serum electrolytes (potassium, calcium, and magnesium) within normal limits. If outside of normal limits, subject will be eligible when electrolytes are corrected;
10. If female, must be either postmenopausal (no menstrual period for a minimum of 12 months), surgically sterile, or if of childbearing potential, must have a negative serum pregnancy test upon entry into this study and must be willing to use maximally effective double-barrier birth control during the period of therapy and contraception for 3 months following the last investigational drug dose;
11. If male, must be surgically sterile or willing to use an effective double-barrier contraception method upon enrollment, during the course of the study, and for 3 months following the last investigational drug dose.

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 BCR-ABL positive leukemia (ie, chronic myelogenous leukemia in blast crisis);
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 or who are 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;
- 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);

** Contact study team for complete eligibility details.

Applicable Disease Sites


Participating Institutions
UF Gainesville : Alina Thompson

Alina Thompson, RN, BSN
Phone: +1 352-273-6841

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