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

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ClinicalTrials.gov Identifier: NCT03552029
Recruitment Status : Recruiting
First Posted : June 11, 2018
Last Update Posted : July 24, 2019
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: Quizartinib Drug: Milademetan Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 156 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description: Part 1 Single Group 1 Arm, Part 2 Parallel, 2 Cohorts
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : August 27, 2018
Estimated Primary Completion Date : October 15, 2021
Estimated Study Completion Date : October 15, 2021


Arm Intervention/treatment
Experimental: Part 1: Quizartinib + Milademetan
Participants with relapsed/refractory FLT3-ITD Mutant AML receive quizartinib + milademetan at increasing and/or decreasing doses and schedules
Drug: Quizartinib
20 or 30 mg tablets for oral administration
Other Names:
  • Experimental product
  • AC220

Drug: Milademetan
5, 20, 80 or 200 mg capsules for oral administration
Other Names:
  • Experimental product
  • DS-3032b

Experimental: Part 2: Cohort 1
Participants with relapsed/refractory FLT3-ITD Mutant AML receive the recommended dose of quizartinib + milademetan determined by Part 1
Drug: Quizartinib
20 or 30 mg tablets for oral administration
Other Names:
  • Experimental product
  • AC220

Drug: Milademetan
30, 45, 80, or 100 mg capsules for oral administration
Other Names:
  • Experimental product
  • DS-3032b

Experimental: Part 2: Cohort 2
Participants with newly diagnosed FLT3-ITD Mutant AML unfit for chemotherapy receive the recommended dose of quizartinib + milademetan determined by Part 1
Drug: Quizartinib
20 or 30 mg tablets for oral administration
Other Names:
  • Experimental product
  • AC220

Drug: Milademetan
30, 45, 80, or 100 mg capsules for oral administration
Other Names:
  • Experimental product
  • DS-3032b




Primary Outcome Measures :
  1. Number of Participants with Dose Limiting Toxicities (DLTs) [ Time Frame: approximately 28 days after start of treatment ]
  2. Number of Participants with Adverse Events (AEs) During the Study [ Time Frame: within approximately 3 years ]
    Adverse events are collected for the entire duration of study participation plus 30 days after the last dose


Secondary Outcome Measures :
  1. Maximum Concentration (Cmax) of Study Drug in Plasma [ Time Frame: within approximately 3 years ]
    Categories: Quizartinib, Metabolite AC886, Milademetan

  2. Area Under the Time-Drug Concentration Curve (AUC) in 24 hours (AUC0-24) [ Time Frame: within approximately 3 years ]
    Categories: Quizartinib, Metabolite AC886, Milademetan

  3. Number of Participants with Response to Treatment [ Time Frame: within approximately 3 years ]
  4. Composite Complete Remission Rate [ Time Frame: within approximately 3 years ]
    Composite complete remission rate is defined as the percentage of participants who achieve CR+CRi+CRh

  5. Partial Remission Rate [ Time Frame: within approximately 3 years ]
    Partial remission rate is defined as the percentage of participants who achieve partial remission (PR)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has reached the age of majority in their country
  • Part 1 (dose escalation): 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
  • Part 2 (dose expansion): 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 prior salvage therapy
  • 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 6 months following the last dose of investigational drug
  • 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 - 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03552029


Locations
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United States, Georgia
Winship Cancer Institute, Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Principal Investigator    404-778-4334    william.g.blum@emory.edu   
United States, Kansas
University of Kansas Cancer Center Recruiting
Fairway, Kansas, United States, 66205
Contact: Principal Investigator    913-588-6078    bskikne@kumc.edu   
United States, Michigan
Rogel Cancer Center, University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Principal Investigator    734-647-2794    dbixby@med.umich.edu   
United States, New York
Roswell Park Comprehensive Cancer Center Recruiting
Buffalo, New York, United States, 14263
Contact: Principal Investigator    716-845-1486    Eunice.Wang@RoswellPark.org   
United States, North Carolina
Duke University Cancer Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Principal Investigator    919-684-8964    harry.erba@duke.edu   
United States, Pennsylvania
Sidney Kimmel Cancer Center, Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Principal Investigator    215-955-8874    margaret.kasner@jefferson.edu   
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Principal Investigator    713-794-4392    NDaver@mdanderson.org   
Sponsors and Collaborators
Daiichi Sankyo, Inc.
Investigators
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Study Director: Clinical Team Leader Daiichi Sankyo, Inc.

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Responsible Party: Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT03552029     History of Changes
Other Study ID Numbers: DS3032-A-U105
2019-001344-22 ( EudraCT Number )
First Posted: June 11, 2018    Key Record Dates
Last Update Posted: July 24, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
URL: https://vivli.org/ourmember/daiichi-sankyo/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Daiichi Sankyo, Inc.:
Relapsed/Refractory
Newly Diagnosed
Unfit for Chemotherapy
Positive for FLT3-ITD Mutation

Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms