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 approximately 24-36 participants in 10-12 study centers in the United States. 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 up to an additional 15 sites worldwide as necessary, based on the enrollment rate, the population, and the standard of care available to them at the time.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: DS-3032b Plus Quizartinib Combination Study in FLT3-ITD Mutant Acute Myeloid Leukemia (AML)
  • Official Title: A Phase 1 Study of DS-3032b 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
  • NCT ID: NCT03552029

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
QuizartinibExperimental product, AC220Part 1: Quizartinib + Milademetan
MilademetanExperimental product, DS-3032bPart 1: Quizartinib + Milademetan

Purpose

Participants with AML that has 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 have a biomarker called FLT3 in their blood. Participants will receive a combined dose of quizartinib and another experimental drug that has 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 quizartinib and DS-3032b 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 approximately 24-36 participants in 10 study centers in the United States. Participants will receive two study drugs (DS-3032b 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 up to an additional 15 sites worldwide as necessary, based on the enrollment rate, the population, and the standard of care available to them at the time.

Trial Arms

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

Eligibility Criteria

        Inclusion Criteria:

          -  Has reached the age of majority in their country

          -  Has FLT3-ITD mutant (> 3% FLT3-ITD/total FLT3) AML (primary AML or secondary to
             myelodysplastic syndrome [MDS]) that have failed any prior induction therapy regimen
             or have relapsed after prior induction/consolidation therapy, have not received more
             than one salvage therapy, and have not received more than one FLT3 inhibitor during
             prior AML treatment(s)

          -  Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

          -  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 3 months following the last dose of investigational drug

          -  Is willing to abstain from grapefruit and Seville oranges (or juice) from 7 days
             before the first dose until study completion

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

        Inclusion Criteria for Cohort 2 in Part 2 only:

          -  FLT3-ITD mutant (> 3% FLT3-ITD/total FLT3) AML (primary AML or secondary to MDS) is
             ineligible for intensive induction chemotherapy by meeting at least 1 of the
             protocol-defined criteria

        Exclusion Criteria:

          -  Has central nervous system (CNS) involvement of leukemia or a history of CNS leukemia

          -  Has acute promyelocytic leukemia (AML subtype M3)

          -  Has uncontrolled or significant cardiovascular disease

          -  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)
Time Frame:approximately 28 days after start of treatment
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
Safety Issue:
Description:Categories: Quizartinib, Metabolite AC886, Milademetan
Measure:Area Under the Time-Drug Concentration Curve (AUC) in 24 hours (AUC0-24)
Time Frame:within approximately 3 years
Safety Issue:
Description:Categories: Quizartinib, Metabolite AC886, Milademetan
Measure:Number of Participants with Response to Treatment
Time Frame:within approximately 3 years
Safety Issue:
Description:
Measure:Composite Complete Remission Rate
Time Frame:within approximately 3 years
Safety Issue:
Description:Composite complete remission rate is defined as the percentage of participants who achieve CR+CRi+CRh
Measure:Partial Remission Rate
Time Frame:within approximately 3 years
Safety Issue:
Description: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 Biomarker

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