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 (1−2 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 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 maintenance 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.
  • 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 an adaptive trial design described in the detailed description
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
All Participants
In an adaptive trial design, participants will receive intrathecal (IT) triple chemotherapy prophylaxis, fludarabine with cytarabine (FLA), daunorubicin, and quizartinib. Some participants might also receive etoposide as part of optional high intensity consolidation with chemotherapy and quizartinib.
  • Drug: Quizartinib
    60 mg powder for solution for oral administration once daily: during dose escalation: at the dose assigned at study entry during dose expansion and maintenance: at the RP2D dose for their age group
    Other names:
    • Quizartinib dihydrochloride
  • Drug: Intrathecal (IT) triple chemotherapy prophylaxis
    IT cytarabine, methotrexate, and either prednisolone or hydrocortisone at doses based on the subject's age and standard practice at each site
    Other names:
    • Standard practice
  • Drug: Fludarabine
    As part of FLA, 30-minute intravenous (IV) infusion of fludarabine on Days 1 through 5 of re-induction Cycles 1 and 2, followed by cytarabine
    Other names:
    • part of FLA
  • Drug: Cytarabine
    As part of FLA, 3-hour IV infusion starting 4 hours after start of fludarabine on Days 1-5 of re-induction Cycles 1 and 2
    Other names:
    • part of FLA
  • Drug: Etoposide
    IV infusion over 3 hours only on Days 1-5 of optional high intensity consolidation with chemotherapy and quizartinib
    Other names:
    • Chemotherapy
  • Drug: Daunorubicin
    120-minute IV infusion on Days 1, 3 and 5 of re-induction Cycle 1 (after FLA)
    Other names:
    • Liposomal daunorubicin (preferred)
    • Conventional daunorubicin (if liposomal not available)
    • Daunoxome (DNX)

Recruiting Locations

Children's National and nearby locations

Children's National Medical Center
Washington, District of Columbia 20010
Contact:
Study Coordinator
202-476-4247
ddelgado@childrensnational.org

More Details

NCT ID
NCT03793478
Status
Recruiting
Sponsor
Daiichi Sankyo, Inc.

Detailed Description

The medical condition being investigated is relapsed or refractory AML in patients 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, using an adaptive trial design. 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.

A. Dose Escalation/De-escalation Phase:

Cohorts of up to 9 participants per dose-level will be enrolled 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 once daily.

B. Dose-Expansion Phase:

Participants will receive the RP2D of quizartinib for their respective age group, administered in combination with re-induction chemotherapy

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

- Intrathecal (IT) triple chemotherapy prophylaxis (given three times)

- In re-induction Cycle 1, fludarabine/cytarabine (FLA) plus daunorubicin (liposomal daunorubicin preferred), followed by quizartinib

- In re-induction Cycle 2, FLA followed by quizartinib as a single agent

C. 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 might 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, as follows:

- High intensity chemotherapy with quizartinib, or

- Low intensity chemotherapy alone, or

- Low intensity therapy with quizartinib as a single agent

D. Maintenance:

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 maintenance therapy at the same dose received during re-induction in the dose expansion phase.

E. Long-term Follow-up:

The long-term follow-up phase begins upon completion of the 12 cycles of quizartinib Maintenance 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 yearly 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.