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

NCT ID: NCT03793478

Last Updated: 2025-08-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

65 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-08-15

Study Completion Date

2027-05-01

Brief Summary

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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.

Detailed Description

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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

Conditions

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Acute Myeloid Leukemia

Study Design

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Allocation Method

NA

Intervention Model

SEQUENTIAL

A single group will progress through a multiple phase study design as described in the detailed description.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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All Participants

All participants will receive re-induction therapy that includes fludarabine and cytarabine in combination with experimental drug quizartinib. For prophylaxis, IT chemotherapy with cytarabine, methotrexate and prednisolone/hydrocortisone will be given prior to or between re-induction cycles. After completing re-induction therapy, eligible participants may also receive optional consolidation chemotherapy which includes cytarabine, etoposide and quizartinib, if HSCT is not available immediately. After completing re-induction or HSCT successfully, eligible participants can go on to receive continuation therapy with quizartinib.

Group Type EXPERIMENTAL

Quizartinib

Intervention Type DRUG

Administered orally once daily starting on Day 6 and continuing through Day 28;

Optional low intensity consolidation with chemotherapy:

Administered orally once daily starting on Day 1 and continuing through Day 28

Fludarabine

Intervention Type DRUG

30 mg/m\^2/day IV infusion given over 30 minutes on Days 1 through 5 (administered based on body weight)

Cytarabine

Intervention Type DRUG

2000 mg/m\^2/day IV infusion given over 3 hours on Days 1 through 5 (begin 4 hours after the start of fludarabine) (administered in accordance with standard of care);

Optional high intensity consolidation with chemotherapy and quizartinib:

500 mg/m\^2/day as a continuous 96-hour IV infusion on Days 1 through 4;

Optional low intensity consolidation with chemotherapy:

75 mg/m\^2/day as once daily subcutaneous or IV on Days 1 through 4 and Days 15 through 18

Intrathecal (IT) triple chemotherapy prophylaxis

Intervention Type DRUG

IT cytarabine, methotrexate, and either prednisolone or hydrocortisone; doses are based on the participant's age and standard practice at each site

Etoposide

Intervention Type DRUG

Optional high intensity consolidation with chemotherapy and quizartinib:

100 mg/m\^2/dose once daily as an IV infusion over 3 hours on Days 1 through 5

Interventions

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Quizartinib

Administered orally once daily starting on Day 6 and continuing through Day 28;

Optional low intensity consolidation with chemotherapy:

Administered orally once daily starting on Day 1 and continuing through Day 28

Intervention Type DRUG

Fludarabine

30 mg/m\^2/day IV infusion given over 30 minutes on Days 1 through 5 (administered based on body weight)

Intervention Type DRUG

Cytarabine

2000 mg/m\^2/day IV infusion given over 3 hours on Days 1 through 5 (begin 4 hours after the start of fludarabine) (administered in accordance with standard of care);

Optional high intensity consolidation with chemotherapy and quizartinib:

500 mg/m\^2/day as a continuous 96-hour IV infusion on Days 1 through 4;

Optional low intensity consolidation with chemotherapy:

75 mg/m\^2/day as once daily subcutaneous or IV on Days 1 through 4 and Days 15 through 18

Intervention Type DRUG

Intrathecal (IT) triple chemotherapy prophylaxis

IT cytarabine, methotrexate, and either prednisolone or hydrocortisone; doses are based on the participant's age and standard practice at each site

Intervention Type DRUG

Etoposide

Optional high intensity consolidation with chemotherapy and quizartinib:

100 mg/m\^2/dose once daily as an IV infusion over 3 hours on Days 1 through 5

Intervention Type DRUG

Other Intervention Names

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Quizartinib dihydrochloride Vanflyta

Eligibility Criteria

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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) 2008 classification with ≥5% blasts in bone marrow, with or without extramedullary disease
* In first relapse or refractory to first-line high-dose chemotherapy with no more than 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 blood as defined in the protocol
* Is between 1 month and 21 years of age at the time the Informed Consent/Assent form is signed
* Has protocol-defined adequate performance status score
* Has fully recovered from the acute clinically significant toxicity effects of all prior 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 highly effective birth control upon enrollment, during the period of therapy, and for 6 months 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 to breast feed
* Male participants must be surgically sterile or willing to use highly effective birth control during the treatment period, and for 6 months following the last dose of quizartinib, etoposide, fludarabine, methotrexate, or cytarabine, whichever is later.
* Participant/legal representative is capable of understanding the investigational nature of the study, potential risks, and benefits, and the patient (and/or legal representative) signs a written assent/informed consent

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 promyelocytic leukemia (APL), juvenile myelomonocytic leukemia, French-American-British classification M3 or WHO classification of APL with translocation, or with myeloid proliferations related to Down syndrome
* Has uncontrolled or pre-defined significant cardiovascular disease as detailed in the protocol
* Has systemic fungal, bacterial, viral or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment. The patient must be off vasopressors and have negative blood cultures for at least 48 hours prior to the start of systematic protocol therapy.
* Has known active clinically relevant liver disease (e.g., active hepatitis B or active 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, or immunotherapy other than as specified in the protocol
* Has any significant concurrent disease, illness, psychiatric disorder or social issue that would compromise subject safety or compliance, interfere with consent/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
Minimum Eligible Age

1 Month

Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Innovative Therapies For Children with Cancer Consortium

OTHER

Sponsor Role collaborator

Children's Oncology Group

NETWORK

Sponsor Role collaborator

Daiichi Sankyo

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Global Clinical Leader

Role: STUDY_DIRECTOR

Daiichi Sankyo

Locations

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Loma Linda University Cancer Center

Loma Linda, California, United States

Site Status

University of California, San Francisco

San Francisco, California, United States

Site Status

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status

A.I. duPont Hospital for Children

Wilmington, Delaware, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

Children's Healthcare of Atlanta

Atlanta, Georgia, United States

Site Status

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

The University of Texas Southwestern Medical Center Children's Health

Dallas, Texas, United States

Site Status

Seattle Children's Hospital

Seattle, Washington, United States

Site Status

Universitair Ziekenhuis Gent

Ghent, , Belgium

Site Status

The Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

British Columbia Children's Hospital

Vancouver, , Canada

Site Status

Rigshospitalet

Copenhagen, , Denmark

Site Status

Centre Léon Bérard

Lyon, , France

Site Status

Hôpital Armand-Trousseau

Paris, , France

Site Status

Hôpital des Enfants

Toulouse, , France

Site Status

Rambam Medical Center

Haifa, , Israel

Site Status

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

Site Status

Fondazione IRCCS San Gerardo dei Tintori

Monza, , Italy

Site Status

IRCCS Ospedale Pediatrico Bambino Gesù

Rome, , Italy

Site Status

Ospedale Infantile Regina Margherita

Torino, , Italy

Site Status

Prinses Maxima Centrum voor Kinderoncologie

Utrecht, , Netherlands

Site Status

Hospital Infantil Universitario Nino Jesus

Madrid, , Spain

Site Status

Hospital Universitario La Paz

Madrid, , Spain

Site Status

Sahlgrenska Universitetssjukhuset - Drottning Silvias Barn- och Ungdomssjukhus

Gothenburg, , Sweden

Site Status

Countries

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United States Belgium Canada Denmark France Israel Italy Netherlands Spain Sweden

Other Identifiers

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2016-002919-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AC220-A-U202

Identifier Type: -

Identifier Source: org_study_id

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