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Safety and Effectiveness of Quizartinib in Children and Young Adults With Acute Myeloid Leukemia (AML), a Cancer of the Blood

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ClinicalTrials.gov Identifier: NCT03793478
Recruitment Status : Recruiting
First Posted : January 4, 2019
Last Update Posted : November 22, 2019
Sponsor:
Collaborators:
Innovative Therapies For Children with Cancer Consortium
Children's Oncology Group
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Brief Summary:

Quizartinib is an experimental drug. It is not approved for regular use. It can only be used in medical research.

Children or young adults with a certain kind of blood cancer (FLT3-ITD AML) might be able to join this study if it has come back after remission, or is not responding to treatment.


Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: Quizartinib Drug: Intrathecal (IT) triple chemotherapy prophylaxis Drug: Fludarabine Drug: Cytarabine Drug: Etoposide Drug: Daunorubicin Phase 1 Phase 2

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 65 participants
Intervention Model: Sequential Assignment
Intervention Model Description: A single group will progress through an adaptive trial design described in the detailed description
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2, Multicenter, Dose-Escalating Study To Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy Of Quizartinib Administered in Combination With Re-Induction Chemotherapy, and as a Single-Agent Maintenance Therapy, in Pediatric Relapsed/Refractory AML Subjects Aged 1 Month to <18 Years (and Young Adults Aged up to 21 Years) With FLT3-ITD Mutations
Actual Study Start Date : August 15, 2018
Estimated Primary Completion Date : May 1, 2027
Estimated Study Completion Date : May 1, 2027


Arm Intervention/treatment
Experimental: All Participants
In an adaptive trial design, participants will receive intrathecal (IT) triple chemotherapy prophylaxis, fludarabine with cytarabine (FLA), daunorubicin, and quizartinib. Some participants might also receive etoposide as part of optional high intensity consolidation with chemotherapy and quizartinib.
Drug: Quizartinib

60 mg powder for solution for oral administration once daily:

  • during dose escalation: at the dose assigned at study entry
  • during dose expansion and maintenance: at the RP2D dose for their age group
Other Name: Quizartinib dihydrochloride

Drug: Intrathecal (IT) triple chemotherapy prophylaxis
IT cytarabine, methotrexate, and either prednisolone or hydrocortisone at doses based on the subject's age and standard practice at each site
Other Name: Standard practice

Drug: Fludarabine
As part of FLA, 30-minute intravenous (IV) infusion of fludarabine on Days 1 through 5 of re-induction Cycles 1 and 2, followed by cytarabine
Other Name: part of FLA

Drug: Cytarabine
As part of FLA, 3-hour IV infusion starting 4 hours after start of fludarabine on Days 1-5 of re-induction Cycles 1 and 2
Other Name: part of FLA

Drug: Etoposide
IV infusion over 3 hours only on Days 1-5 of optional high intensity consolidation with chemotherapy and quizartinib
Other Name: Chemotherapy

Drug: Daunorubicin
120-minute IV infusion on Days 1, 3 and 5 of re-induction Cycle 1 (after FLA)
Other Names:
  • Liposomal daunorubicin (preferred)
  • Conventional daunorubicin (if liposomal not available)
  • Daunoxome (DNX)




Primary Outcome Measures :
  1. Composite complete remission (CRc) rate [ Time Frame: within 8 years, 8 months ]
    CRc rate is defined as percentage of participants with best response of complete remission (CR) or CR with incomplete hematological recovery (CRi) after completion of up to 2 re-induction cycles


Secondary Outcome Measures :
  1. CR rate [ Time Frame: on Day 56 (± 3 Days) for the last subject, within 4 years ]
    CR rate is defined as the percentage of participants achieving CR after completion of up to 2 re-induction cycles

  2. CRi rate [ Time Frame: on Day 56 (± 3 Days) for the last subject, within 4 years ]
    CRi rate is defined as the percentage of participants achieving CRi after completion of up to 2 re-induction cycles

  3. Duration of CR [ Time Frame: within 8 years, 8 months ]
    Duration of CR is defined as the time from the first documented CR until documented relapse

  4. Duration of CRc [ Time Frame: within 8 years, 8 months ]
    Duration of CRc is defined as the time from the first documented CR or CRi until documented relapse

  5. CR rate after completion of re-induction Cycle 1 [ Time Frame: on Day 56 (± 3 Days) for the last subject, within 4 years ]
    CR rate after completion of re-induction Cycle 1 is defined as the percentage of participants achieving a CR after completion of re-induction Cycle 1

  6. CRi rate after completion of re-induction Cycle 1 [ Time Frame: on Day 56 (± 3 Days) for the last subject, within 4 years ]
    CRi rate after completion of re-induction Cycle 1 is defined as the percentage of participants achieving a CRi after completion of re-induction Cycle 1

  7. CRc rate after completion of re-induction Cycle 1 [ Time Frame: on Day 56 (± 3 Days) for the last subject, within 4 years ]
    CRc rate after completion of re-induction Cycle 1 is defined as the percentage of participants achieving CRc after completion of re-induction Cycle 1

  8. Time to Relapse [ Time Frame: within 8 years, 8 months ]
    Time to relapse is defined as the time from the first documented response (CR, CRi) until documented relapse

  9. Rate of Relapse after 1, 2 and 3 years [ Time Frame: within 8 years, 8 months ]
    Rate of relapse is defined as the percentage of participants who achieved CRc at the end of re-induction and had relapsed at 3 categorical time points Categories: 1 year, 2 years, 3 years

  10. Cumulative incidence of relapse at the end of study [ Time Frame: within 8 years, 8 months ]
    Cumulative incidence of relapse at the end of the study is defined as the percentage of participants who achieved CRc at the end of re-induction and relapsed by the end of the study

  11. Overall survival [ Time Frame: within 8 years, 8 months ]
    Overall survival is defined as the time from the start of re-induction therapy until death from any cause

  12. Event-free survival [ Time Frame: within 8 years, 8 months ]

    Event-free survival is defined as the time from the start of re-induction therapy until the earliest date of the following:

    • Refractory disease at the end of re-induction
    • Relapse after CR or CRi
    • Death from any cause at any time during the study

  13. Number of participants proceeding to high-dose conditioning therapy/allogeneic hematopoietic stem cell transplantation (HSCT) [ Time Frame: within 8 years, 8 months ]
  14. Number of participants who achieved CR or CRi with minimal residual disease (MRD) [ Time Frame: within 8 years, 8 months ]

    MRD is defined as the presence of leukemic cells in the bone marrow detected above a predefined cut-off level by a validated assay in participants who achieved a CR or CRi

    Categories: at screening, at re-induction cycle 1, at re-induction cycle 2, at time of relapse


  15. Number of participants who found the quizartinib formulation acceptable [ Time Frame: within 8 years, 8 months ]
    Acceptability is assessed by palatability using a 5-point hedonic scale (from "Super bad" to "Super good") for participants who are developmentally able to answer. If unable, the caregiver provides information in a free text field stating whether the participant spit it out, may not have liked the flavor, etc.



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:   1 Month to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has diagnosis of AML according to the World Health Organization (WHO) 2008 classification with >5% blasts in bone marrow, with or without extramedullary disease
  • Is in first relapse or refractory to first-line high-dose chemotherapy with no more than 1 attempt (1−2 cycles of induction chemotherapy) at remission induction - prior HSCT is permitted
  • Has presence of the FLT3-ITD activating mutation in bone marrow or peripheral blood as defined in the protocol
  • Is between 1 month and 21 years of age at the time the Informed Consent/Assent form is signed
  • Has protocol-defined adequate performance status score
  • Has fully recovered from the acute toxicity effects of all prior chemotherapy, immunotherapy, or radiotherapy, per protocol guidelines
  • Has protocol-defined adequate renal, hepatic and cardiac functions
  • If of reproductive potential, is permanently sterile or agrees to use highly effective birth control upon enrollment, during the period of therapy, and for 6 months following the last dose of study drug or cytarabine, whichever is later
  • If female of child-bearing potential, tests negative for pregnancy and agrees not to breast feed
  • Participant/legal representative is capable of understanding the investigational nature of the study, potential risks, and benefits, and the patient (and/or legal representative) signs a written assent/informed consent
  • Meets protocol-specified guidelines before inclusion in the maintenance phase

Exclusion Criteria:

  • Has been diagnosed with isolated central nervous system relapse, certain kinds of leukemia, or with myeloid proliferations related to Down syndrome
  • Has uncontrolled or pre-defined significant cardiovascular disease as detailed in the protocol
  • Has systemic fungal, bacterial, viral or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment. The patient must be off vasopressors and have negative blood cultures for at least 48 hours.
  • Has known active clinically relevant liver disease (e.g., active hepatitis B or active hepatitis C)
  • Has known history of human immunodeficiency virus (HIV)
  • Has history of hypersensitivity to any of the study medications or their excipients
  • Is receiving or is anticipated to receive concomitant chemotherapy, radiation, or immunotherapy other than as specified in the protocol
  • Has any significant concurrent disease, illness, psychiatric disorder or social issue that would compromise subject safety or compliance, interfere with consent/assent, study participation, follow up, or interpretation of study results
  • Is currently participating in another investigative interventional procedure (observational or long-term interventional follow-up is allowed)
  • Is otherwise considered inappropriate for the study by the Investigator

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): NCT03793478


Locations
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United States, District of Columbia
Children's National Medical Center Recruiting
Washington, District of Columbia, United States, 20010
Contact: Study Coordinator    202-476-4247    ddelgado@childrensnational.org   
Belgium
Universitair Ziekenhuis Gent Recruiting
Gent, Belgium
Contact: Principal Investigator    +32 93326417    barbara.demoeloose@uzgent.be   
Denmark
Rigshospitalet Recruiting
Copenhagen, Denmark, 2100
Contact: Principal Investigator    +45 35450809    karsten.nysom@regionh.dk   
France
Centre Léon Bérard Recruiting
Lyon, France, 69008
Contact: Principal Investigator    +33 469166588    yves.bertrand@ihope.fr   
Hôpital Armand-Trousseau Recruiting
Paris, France, 75012
Contact: Principal Investigator    +33 144736604    arnaud.petit@aphp.fr   
Hôpital des Enfants Recruiting
Toulouse, France, 31300
Contact: Principal Investigator    +33 534558608    pasquet.m@chu-toulouse.fr   
Israel
Rambam Medical Center Recruiting
Haifa, Israel, 31096
Contact: Principal Investigator    +972 502066181    n_arad-cohen@rambam.health.gov.il   
Schneider Children's Medical Center of Israel Recruiting
Petah Tikva, Israel, 49202
Contact: Principal Investigator    +972 39253669    bshlomit@clalit.org.il   
Tel Aviv Sourasky Medical Center Recruiting
Tel Aviv-Yafo, Israel, 64239
Contact: Principal Investigator    +972 36947233    ronite@tlvmc.gov.il   
Italy
Fondazione MBBM - Clinica Pediatrica Recruiting
Monza, Italy, 20900
Contact: Principal Investigator    +39 0392336816    carmelo.rizzari@tiscalinet.it   
Netherlands
Prinses Maxima Centrum voor Kinderoncologie Recruiting
Utrecht, Netherlands, 3584 EA
Contact: Principal Investigator    +31 107036691    c.m.zwaan@erasmusmc.nl   
Spain
Hospital Infantil Universitario Nino Jesus Recruiting
Madrid, Spain, 28009
Contact: Principal Investigator    +34 915035900 ext 672    franciscojose.bautista@salud.madrid.org   
Hospital Universitario La Paz Recruiting
Madrid, Spain, 28046
Contact: Principal Investigator    +34 912071876    aperezmartinez@salud.madrid.org   
Sweden
Sahlgrenska Universitetssjukhuset - Drottning Silvias Barn- och Ungdomssjukhus Recruiting
Göteborg, Sweden, 41685
Contact: Principal Investigator    +46 707695159    Jonas.abrahamsson@vgregion.se   
Sponsors and Collaborators
Daiichi Sankyo, Inc.
Innovative Therapies For Children with Cancer Consortium
Children's Oncology Group
Investigators
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Study Director: Global Clinical Leader Daiichi Sankyo, Inc.

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Responsible Party: Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT03793478     History of Changes
Other Study ID Numbers: AC220-A-U202
2016-002919-18 ( EudraCT Number )
First Posted: January 4, 2019    Key Record Dates
Last Update Posted: November 22, 2019
Last Verified: November 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.:
Acute myeloid leukemia recurrent
Relapsed or refractory
FMS-like tyrosine kinase 3 positive
Cancer of the blood
AML
FLT3-ITD mutation
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Fludarabine
Fludarabine phosphate
Etoposide
Etoposide phosphate
Daunorubicin
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antiviral Agents
Anti-Infective Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antibiotics, Antineoplastic