Safety and Efficacy of Quizartinib in Children and Young Adults With Acute Myeloid Leukemia (AML), a Cancer of the Blood

Last updated: January 16, 2025
Sponsor: Daiichi Sankyo
Overall Status: Active - Not Recruiting

Phase

1/2

Condition

Leukemia

Acute Myeloid Leukemia

Platelet Disorders

Treatment

Etoposide

Cytarabine

Quizartinib

Clinical Study ID

NCT03793478
AC220-A-U202
2016-002919-18
  • Ages 1-21
  • All Genders

Study Summary

Quizartinib is an experimental drug. It is not approved for regular use. It can only be used in medical research.

Children or young adults with a certain kind of blood cancer (FLT3-ITD AML) might be able to join this study if it has come back after remission or is not responding to treatment.

Eligibility Criteria

Inclusion

Inclusion Criteria:

Participants must meet all of the following criteria to be eligible for enrollment into the study:

  • Has diagnosis of AML according to the World Health Organization (WHO) 2008classification with ≥5% blasts in bone marrow, with or without extramedullarydisease

  • In first relapse or refractory to first-line high-dose chemotherapy with no morethan 1 attempt (1 to 2 cycles of induction chemotherapy) at remission induction -prior HSCT is permitted

  • Has presence of the FLT3-ITD activating mutation in bone marrow or peripheral bloodas defined in the protocol

  • Is between 1 month and 21 years of age at the time the Informed Consent/Assent formis signed

  • Has protocol-defined adequate performance status score

  • Has fully recovered from the acute clinically significant toxicity effects of allprior chemotherapy, immunotherapy, or radiotherapy, per protocol guidelines

  • Has protocol-defined adequate renal, hepatic and cardiac functions

  • If of reproductive potential, is permanently sterile or agrees to use highlyeffective birth control upon enrollment, during the period of therapy, and for 6months following the last dose of quizartinib, etoposide, fludarabine, methotrexate,or cytarabine, whichever is later

  • If female of child-bearing potential, tests negative for pregnancy and agrees not tobreast feed

  • Male participants must be surgically sterile or willing to use highly effectivebirth control during the treatment period, and for 6 months following the last doseof quizartinib, etoposide, fludarabine, methotrexate, or cytarabine, whichever islater.

  • Participant/legal representative is capable of understanding the investigationalnature of the study, potential risks, and benefits, and the patient (and/or legalrepresentative) signs a written assent/informed consent

Exclusion

Exclusion Criteria:

Participants who meet any of the following criteria will be disqualified from entering the study:

  • Has been diagnosed with isolated central nervous system relapse, acute promyelocyticleukemia (APL), juvenile myelomonocytic leukemia, French-American-Britishclassification M3 or WHO classification of APL with translocation, or with myeloidproliferations related to Down syndrome

  • Has uncontrolled or pre-defined significant cardiovascular disease as detailed inthe protocol

  • Has systemic fungal, bacterial, viral or other infection that is exhibiting ongoingsigns/symptoms related to the infection without improvement despite appropriateantibiotics or other treatment. The patient must be off vasopressors and havenegative blood cultures for at least 48 hours prior to the start of systematicprotocol therapy.

  • Has known active clinically relevant liver disease (e.g., active hepatitis B oractive hepatitis C)

  • Has known history of human immunodeficiency virus (HIV)

  • Has history of hypersensitivity to any of the study medications or their excipients

  • Is receiving or is anticipated to receive concomitant chemotherapy, radiation, orimmunotherapy other than as specified in the protocol

  • Has any significant concurrent disease, illness, psychiatric disorder or socialissue that would compromise subject safety or compliance, interfere withconsent/assent, study participation, follow up, or interpretation of study results

  • Is currently participating in another investigative interventional procedure (observational or long-term interventional follow-up is allowed)

  • Is otherwise considered inappropriate for the study by the Investigator

Study Design

Total Participants: 65
Treatment Group(s): 5
Primary Treatment: Etoposide
Phase: 1/2
Study Start date:
August 15, 2018
Estimated Completion Date:
May 01, 2027

Study Description

The medical condition being investigated is relapsed or refractory AML in participants aged ≥1 month to ≤21 years with Feline McDonough Sarcoma (FMS)-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) mutations (FLT3-ITD AML), following failure of front-line intensive chemotherapy.

The trial will be conducted in multiple phases. An independent data monitoring committee (DMC) will protect the rights, safety, and well-being of participants by monitoring the progress and results. The DMC will comprise qualified physicians and scientists who are not Investigators in the study and not otherwise directly associated with the Sponsor and will be convened at the end of Phase 1.

A. Dose Escalation/De-escalation Phase:

Number of participants is determined by age group. Participants will be enrolled by dose-level to determine the recommended Phase 2 dose (RP2D) of quizartinib for pediatric participants that provides similar exposure to adult patients treated at the target adult dose of 60 mg orally once daily.

B. Dose-Expansion Phase:

Participants will receive the RP2D of quizartinib for their respective age group.

During both dose escalation and dose expansion phases, participants will receive:

Re-Induction Therapy

  • Intrathecal (IT) triple chemotherapy prophylaxis prior to and between cycles

  • In re-induction Cycles 1 and 2, fludarabine/cytarabine (FLA) followed by quizartinib as a single agent

Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) Period:

After re-induction therapy, participants will be evaluated for eligibility to undergo allogeneic hematopoietic stem cell transplant (HSCT). Eligible participants may receive a single 28-day cycle of consolidation therapy (standard of care chemotherapy with or without quizartinib) if an allogeneic HSCT is not available immediately. The options for consolidation therapy are as follows:

  • High intensity chemotherapy with quizartinib, or

  • Low intensity chemotherapy alone, or

  • Low intensity therapy with quizartinib as a single agent

Continuation Therapy:

Participants in remission after HSCT, or who are not eligible for HSCT but achieve at least a partial remission (PR) after re-induction, will receive up to 12 continuous 28-day cycles of quizartinib continuation therapy at the same dose received during re-induction in the dose expansion phase.

Long-term Follow-up:

The long-term follow-up phase begins upon completion of 12 cycles of quizartinib Continuation Therapy or permanent discontinuation of quizartinib at any time. After completion of the 30-day safety follow-up visit, subsequent visits will occur at the following frequencies to assess survival and anti-leukemic treatments:

  • every 3 months for the first 2 years, and then

  • once a year thereafter until the last participant enrolled has been followed for three years from the date of enrollment

Connect with a study center

  • Universitair Ziekenhuis Gent

    Gent,
    Belgium

    Site Not Available

  • The Hospital for Sick Children

    Toronto, Ontario M5G1X8
    Canada

    Site Not Available

  • Montreal Children's Hospital

    Montréal, Quebec H4A3J1
    Canada

    Site Not Available

  • British Columbia Children's Hospital

    Vancouver, V6H 3V4
    Canada

    Site Not Available

  • Rigshospitalet

    Copenhagen, 2100
    Denmark

    Site Not Available

  • Centre Léon Bérard

    Lyon, 69008
    France

    Site Not Available

  • Hôpital Armand-Trousseau

    Paris, 75012
    France

    Site Not Available

  • Hôpital des Enfants

    Toulouse, 31300
    France

    Site Not Available

  • Rambam Medical Center

    Haifa, 31096
    Israel

    Site Not Available

  • Schneider Children's Medical Center of Israel

    Petah Tikva, 49202
    Israel

    Site Not Available

  • Tel Aviv Sourasky Medical Center

    Tel Aviv-Yafo, 64239
    Israel

    Site Not Available

  • Fondazione IRCCS San Gerardo dei Tintori

    Monza, 20900
    Italy

    Site Not Available

  • Fondazione MBBM - Clinica Pediatrica

    Monza, 20900
    Italy

    Active - Recruiting

  • IRCCS Ospedale Pediatrico Bambino Gesù

    Rome, 00165
    Italy

    Site Not Available

  • Ospedale Infantile Regina Margherita

    Torino, 10126
    Italy

    Site Not Available

  • Prinses Maxima Centrum voor Kinderoncologie

    Utrecht, 3584 EA
    Netherlands

    Site Not Available

  • Hospital Infantil Universitario Nino Jesus

    Madrid, 28009
    Spain

    Site Not Available

  • Hospital Universitario La Paz

    Madrid, 28046
    Spain

    Site Not Available

  • Sahlgrenska Universitetssjukhuset - Drottning Silvias Barn- och Ungdomssjukhus

    Göteborg, 41685
    Sweden

    Site Not Available

  • NHS Greater Glasgow and Clyde - The Queen Elizabeth University Hospital

    Glasgow, G51 4TF
    United Kingdom

    Site Not Available

  • Loma Linda University Cancer Center

    Loma Linda, California 92354
    United States

    Site Not Available

  • University of California, San Francisco

    San Francisco, California 94158
    United States

    Site Not Available

  • Children's Hospital Colorado

    Aurora, Colorado 80045
    United States

    Site Not Available

  • A.I. duPont Hospital for Children

    Wilmington, Delaware 19803
    United States

    Site Not Available

  • Children's National Medical Center

    Washington, District of Columbia 20010
    United States

    Site Not Available

  • Children's Healthcare of Atlanta

    Atlanta, Georgia 30322
    United States

    Site Not Available

  • Riley Hospital for Children - Indiana University

    Indianapolis, Indiana 46202
    United States

    Site Not Available

  • Johns Hopkins

    Baltimore, Maryland 21287
    United States

    Site Not Available

  • University of Minnesota/Masonic Cancer Center

    Minneapolis, Minnesota 55455
    United States

    Site Not Available

  • University of Mississippi Medical Center

    Jackson, Mississippi 39216
    United States

    Site Not Available

  • Washington University School of Medicine

    Saint Louis, Missouri 63110
    United States

    Site Not Available

  • Columbia University/Herbert Irving Cancer Center

    New York, New York 10032
    United States

    Site Not Available

  • New York Medical College

    Valhalla, New York 10595
    United States

    Site Not Available

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio 45229
    United States

    Site Not Available

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania 19104
    United States

    Site Not Available

  • UPMC Children's Hospital of Pittsburgh

    Pittsburgh, Pennsylvania 15224
    United States

    Site Not Available

  • The University of Texas Southwestern Medical Center Children's Health

    Dallas, Texas 75390
    United States

    Site Not Available

  • Seattle Children's Hospital

    Seattle, Washington 98105
    United States

    Site Not Available

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.