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

Official Title

A Phase 1/2, Multicentre, Dose-Escalating Study To Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy Of Quizartinib Administered in Combination With Re-Induction Chemotherapy, and as a Single-Agent Continuation Therapy, in Pediatric Relapsed/Refractory AML Subjects Aged 1 Month to <18 Years (and Young Adults Aged up to 21 Years) With FLT3-ITD Mutations

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.

Trial Description

Primary Outcome:

• Composite complete remission (CRc) rate among participants with acute myeloid leukemia (AML)

Secondary Outcome:

• Complete remission (CR) rate among participants with acute myeloid leukemia (AML)
• Complete remission with incomplete recovery (CRi) rate among participants with acute myeloid leukemia (AML)
• Duration of complete remission (CR) among participants with acute myeloid leukemia (AML)
• Duration of complete remission with incomplete recovery (CRi) among participants with acute myeloid leukemia (AML)
• Duration of composite complete remission (CRc) among participants with acute myeloid leukemia (AML)
• Complete remission (CR) rate after completion of re-induction Cycle 1 among participants with acute myeloid leukemia (AML)
• Complete remission with incomplete recovery (CRi) rate after completion of re-induction Cycle 1 among participants with acute myeloid leukemia (AML)
• Composite complete remission (CRc) rate after completion of re-induction Cycle 1 among participants with acute myeloid leukemia (AML)
• Time to relapse among participants with acute myeloid leukemia (AML)
• Rate of relapse among participants with acute myeloid leukemia (AML) after 1, 2 and 3 years
• Cumulative incidence of relapse among participants with acute myeloid leukemia (AML) at the end of study
• Overall survival among participants with acute myeloid leukemia (AML)
• Event-free survival among participants with acute myeloid leukemia (AML)
• Number of participants proceeding to high-dose conditioning therapy/allogeneic hematopoietic stem cell transplantation (HSCT) (including transplant-related mortality) among participants with acute myeloid leukemia (AML)
• Rate of composite complete remission (CRc; complete remission [CR] or complete remission with incomplete recovery [CRi]) without minimal residual disease (MRD) using next generation sequencing among participants with acute myeloid leukemia (AML)
• Acceptability of including the palatability of quizartinib formulations among participants with acute myeloid leukemia (AML): 5-point hedonic scale

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

View this trial on ClinicalTrials.gov