Purpose

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.

Condition

Eligibility

Eligible Ages
Between 1 Month and 21 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Has diagnosis of AML according to the World Health Organization (WHO) 2008 classification with >5% blasts in bone marrow, with or without extramedullary disease
  • Is 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 study drug or cytarabine, whichever is later
  • If female of child-bearing potential, tests negative for pregnancy and agrees not to breast feed
  • 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
  • Meets protocol-specified guidelines before inclusion in the continuation therapy phase

Exclusion Criteria

  • Has been diagnosed with isolated central nervous system relapse, certain kinds of leukemia, 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

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Intervention Model
Sequential Assignment
Intervention Model Description
A single group will progress through a multiple phase study design as described in the detailed description.
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
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.
  • Drug: Quizartinib
    Administered orally once daily starting on Day 6 and continuing through Day 28
    Other names:
    • Quizartinib dihydrochloride
    • Vanflyta
  • 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
  • Drug: Fludarabine
    30 mg/m^2/day IV infusion given over 30 minutes on Days 1 through 5 (administered based on body weight)
  • 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) or 500 mg/m^2/day as a continuous 96-hour IV infusion on Days 1 through (administered based on body weight as optional high intensity consolidation therapy).
  • Drug: Etoposide
    100 mg/m^2/dose once daily as an IV infusion over 3 hours on Days 1 through 5 (administered based on body weight as optional high intensity consolidation therapy)

Recruiting Locations

Children's National and nearby locations

Children's National Medical Center
Washington, District of Columbia 20010
Contact:
Study Coordinator

More Details

NCT ID
NCT03793478
Status
Recruiting
Sponsor
Daiichi Sankyo, Inc.

Study Contact

Daiichi Sankyo Contact for Clinical Information
908-992-6400
CTRinfo@dsi.com

Detailed 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

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.