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(QuANTUM-R): An Open-label Study of Quizartinib Monotherapy vs. Salvage Chemotherapy in Acute Myeloid Leukemia (AML) Subjects Who Are FLT3-ITD Positive

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02039726
Recruitment Status : Completed
First Posted : January 20, 2014
Results First Posted : January 27, 2020
Last Update Posted : February 24, 2021
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo

Study Description
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Brief Summary:
The primary objective of the study is to determine whether quizartinib monotherapy prolongs overall survival (OS) compared to salvage chemotherapy in subjects with FMS-like tyrosine kinase 3 - Internal Tandem Duplication (FLT3-ITD) positive AML who are refractory to or have relapsed within 6 months, after first-line AML therapy.

Condition or disease Intervention/treatment Phase
AML Drug: Quizartinib Drug: Salvage Chemotherapy Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 367 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3 Open-label Randomized Study of Quizartinib (AC220) Monotherapy Versus Salvage Chemotherapy in Subjects With Tyrosine Kinase 3 - Internal Tandem Duplication (FLT3-ITD) Positive Acute Myeloid Leukemia (AML) Refractory to or Relapsed After First-line Treatment With or Without Hematopoietic Stem Cell Transplantation (HSCT) Consolidation
Actual Study Start Date : May 2014
Actual Primary Completion Date : February 22, 2018
Actual Study Completion Date : September 8, 2020

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Arms and Interventions
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Arm Intervention/treatment
Experimental: Quizartinib
Participants who were randomized to receive 20 or 30 mg quizartinib tablets administered orally once daily.
 Drug: Quizartinib
20 or 30 mg quizartinib tablets administered orally once daily
Other Name: AC220
Active Comparator: Salvage chemotherapy
Participants who were randomized to receive salvage chemotherapy, such as low dose cytarabine (LoDAC); mitoxantrone, etoposide, and intermediate-dose cytarabine (MEC); or fludarabine, cytarabine, and granulocyte colony stimulating factor (G-CSF) with idarubicin (FLAG-IDA), were administered during 28-day cycles.
 Drug: Salvage Chemotherapy
Low dose cytarabine (LoDAC); mitoxantrone, etoposide, and intermediate-dose cytarabine (MEC); or fludarabine, cytarabine, and granulocyte colony stimulating factor (G-CSF) with idarubicin (FLAG-IDA) administered during 28-day cycles
Other Name: Standard of Care


Outcome Measures
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Primary Outcome Measures :
  1. Overall Survival in Participants That Received Quizartinib Versus Salvage Chemotherapy [ Time Frame: At approximately 3 years 9 months ]
    Overall Survival is defined as the time (in weeks) from the date of randomization to the date of death due to any cause. Median and quartiles are calculated using the Kaplan-Meier method.


Secondary Outcome Measures :
  1. Event-free Survival in Participants That Received Quizartinib Versus Salvage Chemotherapy [ Time Frame: At approximately 3 years 9 months ]
    Event-free survival is defined as the time (in weeks) from randomization until documented refractory disease, relapse after complete composite remission (CRc), or death from any cause, whichever is observed first.


Eligibility Criteria
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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:

  1. Provision of written informed consent approved by the Institutional Review Board (IRB) or Independent Ethics Committee (IEC) with privacy language in accordance with national regulations (e.g., Health Insurance Portability and Accountability Act [HIPAA] authorization for United States [US] sites) prior to any study related procedures, including withdrawal of prohibited medications if applicable.
  2. Age ≥ 18 years or the minimum legal adult age (whichever is greater) at the time of Informed consent.
  3. Morphologically documented primary Acute Myeloid Leukemia (AML) or AML secondary to Myelodysplastic Syndrome (MDS), as defined by World Health Organization (WHO) criteria, as determined by pathology review at the study site.
  4. In first relapse (with duration of remission of 6 months or less) or refractory after prior therapy, with or without HSCT. Induction therapy must have included at least 1 cycle of an anthracycline/mitoxantrone-containing induction block at a standard dose.
  5. Presence of the FLT3-ITD activating mutation in bone marrow or peripheral blood (allelic ratio as determined by a central laboratory with a cutoff of ≥3% FLT3-ITD/total FLT3). If a specimen has been sent for FLT3-ITD testing at the central laboratory but the subject requires treatment for AML before the central FLT3-ITD test result is available, a local test result may be acceptable for randomization after consultation with the Medical Monitor.
  6. Eligibility for pre-selected salvage chemotherapy, according to the Investigator's assessment.
  7. Eastern Cooperative Oncology Group (ECOG) performance score 0-2.
  8. Discontinuation of prior AML treatment before the start of study treatment (except hydroxyurea or other treatment to control leukocytosis) for at least 2 weeks for cytotoxic agents, or for at least 5 half-lives for non cytotoxic agents.
  9. Serum creatinine ≤1.5×upper limit of normal (ULN), or glomerular filtration rate >25 mL/min, as calculated with the Cockcroft-Gault formula.
  10. Serum potassium, magnesium, and calcium (serum calcium corrected for hypoalbuminemia) within institutional normal limits. Subjects with electrolytes outside the normal range will be eligible if these values are corrected upon retesting following any necessary supplementation.
  11. Total serum bilirubin ≤1.5×ULN.
  12. Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) ≤2.5×ULN.

Exclusion Criteria:

  1. Acute Promyelocytic Leukemia (AML subtype M3).
  2. AML secondary to prior chemotherapy for other neoplasms, except AML secondary to prior Myelodysplastic Syndrome (MDS).
  3. History of another malignancy, unless the candidate has been disease-free for at least 5 years.
  4. Persistent, clinically significant > Grade 1 non-hematologic toxicity from prior AML therapy.
  5. Clinically significant graft versus host disease (GVHD) or GVHD requiring initiation of treatment or treatment escalation within 21 days, and/or > Grade 1 persistent or clinically significant non hematologic toxicity related to HSCT.
  6. History of or current, central nervous system involvement with AML.
  7. Clinically significant coagulation abnormality, such as disseminated intravascular coagulation.
  8. Prior treatment with quizartinib or participated in a prior quizartinib study.
  9. Prior treatment with a FLT3 targeted therapy including sorafenib or investigational FLT3 inhibitors (not including the multi-kinase inhibitor, midostaurin).
  10. Major surgery within 4 weeks prior to screening.
  11. Radiation therapy within 4 weeks prior to screening.
  12. Uncontrolled or significant cardiovascular disease
  13. Active infection not well controlled by antibacterial or antiviral therapy.
  14. Known infection with human immunodeficiency virus, or active hepatitis B or C, or other active clinically relevant liver disease.
  15. Unwillingness to receive infusion of blood products according to the protocol.
  16. In a man whose sexual partner is a woman of childbearing potential, unwillingness or inability of the man or woman to use a highly effective contraceptive method for the entire study treatment period for at least 3 months after study completion. Male subjects must not freeze or donate sperm starting at Screening and throughout the study period, and 105 days after the final study drug administration.
  17. In a heterosexually active woman of childbearing potential, unwillingness or inability to use a highly effective contraceptive method for the entire study treatment period and for at least 3 months after study treatment completion. Additionally, for women randomized to chemotherapy, unwillingness to adhere to the restrictions in the respective locally established guidelines and local approved label (prescribing information, Summary of Product Characteristics, or US product insert) from the manufacturer and the Patient Information Leaflet (package insert) as instructed by the Investigator.
  18. Pregnancy.
  19. Female Subjects must agree to not breastfeed from the time of Screening and throughout the study period, and for 25 days after the final study drug administration.
  20. Medical condition, serious intercurrent illness, or other circumstance that, in the Investigator's judgment, could jeopardize the candidate's safety as a study subject, or that could interfere with study objectives.
  21. For subjects in the United Kingdom only: Refusal of permission to allow the subject's General Practitioner to be notified of their participation in the study.
Contacts and Locations
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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): NCT02039726


Locations
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Sponsors and Collaborators
Daiichi Sankyo
Investigators
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Principal Investigator: Jorge E. Cortes, MD M.D. Anderson Cancer Center
Study Director: Global Clinical Leader Daiichi Sankyo
  Study Documents (Full-Text)

Documents provided by Daiichi Sankyo:
Study Protocol and Statistical Analysis Plan  [PDF] June 30, 2017

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Daiichi Sankyo
ClinicalTrials.gov Identifier: NCT02039726    
Other Study ID Numbers: AC220-007
EudraCT Number 2013-004890-28 ( Other Identifier: Universal Trial Number (UTN) U1111-1151-8078 )
First Posted: January 20, 2014    Key Record Dates
Results First Posted: January 27, 2020
Last Update Posted: February 24, 2021
Last Verified: February 2021
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/
Keywords provided by Daiichi Sankyo:
Acute Myeloid Leukemia
AML
FMS-like tyrosine kinase 3
FLT3-ITD
 Quizartinib
Leukemia
Tablets
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Hematologic Diseases
 Quizartinib
Tyrosine Kinase Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action