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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 : Active, not recruiting
First Posted : January 20, 2014
Results First Posted : January 27, 2020
Last Update Posted : February 10, 2020
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Tracking Information
First Submitted Date  ICMJE January 15, 2014
First Posted Date  ICMJE January 20, 2014
Results First Submitted Date  ICMJE September 25, 2019
Results First Posted Date  ICMJE January 27, 2020
Last Update Posted Date February 10, 2020
Actual Study Start Date  ICMJE May 2014
Actual Primary Completion Date February 22, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 24, 2020)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: January 16, 2014)
Overall Survival [ Time Frame: 1 year ]
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 (FLT3-ITD) positive Acute Myeloid Leukemia (AML) who are refractory to or have relapsed within 6 months, after first-line Acute Myeloid Leukemia (AML) therapy.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 24, 2020)
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.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 16, 2014)
Event-Free Survival [ Time Frame: 1 year ]
The secondary objective is to determine event-free survival (EFS) with quizartinib versus salvage chemotherapy.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE (QuANTUM-R): An Open-label Study of Quizartinib Monotherapy vs. Salvage Chemotherapy in Acute Myeloid Leukemia (AML) Subjects Who Are FLT3-ITD Positive
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE AML
Intervention  ICMJE
  • Drug: Quizartinib
    20 or 30 mg quizartinib tablets administered orally once daily
    Other Name: AC220
  • 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
Study Arms  ICMJE
  • Experimental: Quizartinib
    Participants who were randomized to receive 20 or 30 mg quizartinib tablets administered orally once daily.
    Intervention: Drug: Quizartinib
  • 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.
    Intervention: Drug: Salvage Chemotherapy
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: September 25, 2017)
367
Original Estimated Enrollment  ICMJE
 (submitted: January 16, 2014)
326
Estimated Study Completion Date  ICMJE December 2020
Actual Primary Completion Date February 22, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Canada,   Croatia,   Czechia,   France,   Germany,   Hong Kong,   Hungary,   Italy,   Korea, Republic of,   Netherlands,   Poland,   Serbia,   Singapore,   Spain,   Taiwan,   United Kingdom,   United States
Removed Location Countries China,   Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT02039726
Other Study ID Numbers  ICMJE AC220-007
EudraCT Number 2013-004890-28 ( Other Identifier: Universal Trial Number (UTN) U1111-1151-8078 )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
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
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: 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/
Responsible Party Daiichi Sankyo, Inc.
Study Sponsor  ICMJE Daiichi Sankyo, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jorge E. Cortes, MD M.D. Anderson Cancer Center
Study Director: Global Clinical Leader Daiichi Sankyo, Inc.
PRS Account Daiichi Sankyo, Inc.
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP