Clinical Trials /

Milademetan Plus Quizartinib Combination Study in FLT3-ITD Mutant Acute Myeloid Leukemia (AML)

NCT03552029

Description:

Participants with AML that have gone into remission and come back (relapsed) or gone into remission with a number of leukemia cells still in their system (refractory) will be recruited for this study. They will also be positive for FLT3-ITD mutation. Participants will receive a combined dose of quizartinib and milademetan that have not been approved by the US Food and Drug Administration yet (m). The combination of these drugs will be provided in different amounts on defined days (dosing schedules). It is expected that the combination of milademetan and quizartinib will be safe and well tolerated. It is expected that the combination may fight the leukemia better than a single drug. The study will run for approximately 3 years. There may be up to 156 participants. The study has 2 parts: - Part 1 will test 24-36 participants in approximately 15 study centers globally. Participants will receive two study drugs (milademetan and quizartinib) in different amounts on specific days. Information will be gathered to see what dosing schedule of the drug combination is best (maximum tolerated/recommended dose). - Part 2 of the study will confirm the recommended dosing schedule identified in Part 1 is effective. A larger number of participants will receive the recommended dose in approximately 15 additional sites worldwide as necessary, based on the enrollment rate, the population, and the standard of care available to them at the time of enrollment.

Related Conditions:
  • Acute Myeloid Leukemia
  • Secondary Acute Myeloid Leukemia
  • Therapy-Related Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Milademetan Plus Quizartinib Combination Study in FLT3-ITD Mutant Acute Myeloid Leukemia (AML)
  • Official Title: A Phase 1 Study of Milademetan in Combination With Quizartinib in Subjects With FLT3-ITD Mutant Acute Myeloid Leukemia That Are Relapsed/Refractory, or Newly Diagnosed and Unfit for Intensive Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: DS3032-A-U105
  • SECONDARY ID: 2019-001344-22
  • NCT ID: NCT03552029

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
QuizartinibAC220, VanflytaPart 1 - Quizartinib + Milademetan
MilademetanDS-3032bPart 1 - Quizartinib + Milademetan
MilademetanDS-3032bPart 2 - Cohort 1

Purpose

Participants with AML that have gone into remission and come back (relapsed) or gone into remission with a number of leukemia cells still in their system (refractory) will be recruited for this study. They will also be positive for FLT3-ITD mutation. Participants will receive a combined dose of quizartinib and milademetan that have not been approved by the US Food and Drug Administration yet (m). The combination of these drugs will be provided in different amounts on defined days (dosing schedules). It is expected that the combination of milademetan and quizartinib will be safe and well tolerated. It is expected that the combination may fight the leukemia better than a single drug. The study will run for approximately 3 years. There may be up to 156 participants. The study has 2 parts: - Part 1 will test 24-36 participants in approximately 15 study centers globally. Participants will receive two study drugs (milademetan and quizartinib) in different amounts on specific days. Information will be gathered to see what dosing schedule of the drug combination is best (maximum tolerated/recommended dose). - Part 2 of the study will confirm the recommended dosing schedule identified in Part 1 is effective. A larger number of participants will receive the recommended dose in approximately 15 additional sites worldwide as necessary, based on the enrollment rate, the population, and the standard of care available to them at the time of enrollment.

Trial Arms

NameTypeDescriptionInterventions
Part 1 - Quizartinib + MilademetanExperimentalParticipants with relapsed/refractory FLT3-ITD Mutant AML receive quizartinib + milademetan at increasing and/or decreasing doses and schedules
  • Quizartinib
  • Milademetan
Part 2 - Cohort 1ExperimentalParticipants with relapsed/refractory FLT3-ITD Mutant AML receive the recommended dose of quizartinib + milademetan determined by Part 1
  • Quizartinib
  • Milademetan
Part 2 - Cohort 2ExperimentalParticipants with newly diagnosed FLT3-ITD Mutant AML unfit for chemotherapy receive the recommended dose of quizartinib + milademetan determined by Part 1
  • Quizartinib
  • Milademetan

Eligibility Criteria

        Inclusion Criteria:

          -  Has reached ≥18 years old or the age of the age of majority in their country

          -  Part 1 (dose escalation): Has FLT3-ITD mutant (≥ 3% FLT3-ITD/total FLT3) AML (primary
             AML, secondary, or therapy-related AML), and has treatment failure to prior AML
             therapy or have relapsed after prior AML therapy

          -  Part 2 (dose expansion): Has FLT3-ITD mutant (≥3% FLT3-ITD/total FLT3) AML (primary,
             secondary, or therapy-related AML), and has treatment failure to prior AML therapy or
             have relapsed after prior AML therapy, OR has newly diagnosed AML who are ineligible
             for intensive induction chemotherapy

          -  Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (or 3 for
             patients with newly diagnosed AML between 18 and 74 years old)

          -  Has protocol-defined adequate renal, hepatic and cardiac status

          -  Is not pregnant, and if not postmenopausal or a surgically sterile male or female, is
             willing to use a highly effective contraceptive method upon enrollment, during the
             course of the study, and for 6 months following the last dose of investigational drug

          -  Is able and willing to provide protocol-defined bone marrow biopsies/aspirates

        Exclusion Criteria:

          -  Has central nervous system (CNS) involvement of leukemia - patients with a history of
             CNS leukemia may be eligible if the CNS leukemia is adequately controlled (defined as
             no clinical symptoms of CNS disease and at least 2 consecutive lumbar punctures with
             no evidence of disease prior to study enrollment) after discussion and approval from
             the Sponsor

          -  Has acute promyelocytic leukemia (AML subtype M3)

          -  Has uncontrolled or significant cardiovascular disease or QTc interval >450 ms
             (average of triplicate determination)

          -  Has an uncontrolled infection requiring intravenous antibiotics, antivirals, or
             antifungals.

          -  Has known human immunodeficiency virus (HIV) infection, or active hepatitis B or C
             infection based on positive tests during Screening

          -  Has persistent, clinically significant > Grade 1 non-hematologic toxicity from prior
             AML therapies

          -  Has any history or medical condition, metastatic condition, drug/medication use or
             other condition that might, per protocol or in the opinion of the investigator,
             compromise:

               1. safety or well-being of the participant or offspring

               2. safety of study staff

               3. analysis of results
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants with Dose Limiting Toxicities (DLTs) (Part 1 only)
Time Frame:within approximately 18 months from start of study
Safety Issue:
Description:Adverse events are collected for the entire duration of study participation plus 30 days after the last dose

Secondary Outcome Measures

Measure:Maximum Concentration (Cmax) of Study Drug in Plasma
Time Frame:within approximately 3 years from start of study
Safety Issue:
Description:Categories: Quizartinib, Metabolite AC886, Milademetan
Measure:Number of Participants with Response to Treatment (Part 1 only)
Time Frame:within approximately 18 months from start of study
Safety Issue:
Description:Composite complete remission rate is defined as the percentage of participants who achieve CR+CRi+CRh. Partial remission rate is defined as the percentage of participants who achieve partial remission (PR).

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Daiichi Sankyo, Inc.

Trial Keywords

  • Relapsed/Refractory
  • Newly Diagnosed
  • Unfit for Chemotherapy
  • Positive for FLT3-ITD Mutation

Last Updated

July 20, 2020