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

Summary

Objectives

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