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Trial record 1 of 2 for:    asp2215 flt3/itd aml
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A Study of ASP2215 (Gilteritinib), Administered as Maintenance Therapy Following Induction/Consolidation Therapy for Subjects With FMS-like Tyrosine Kinase 3 (FLT3/ITD) Acute Myeloid Leukemia (AML) in First Complete Remission

This study is currently recruiting participants.
Verified November 2017 by Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
Sponsor:
ClinicalTrials.gov Identifier:
NCT02927262
First Posted: October 7, 2016
Last Update Posted: December 1, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
  Purpose
The purpose of this study is to compare relapse-free survival (RFS) between subjects with FMS-like tyrosine kinase 3 (FLT3) / internal tandem duplication (ITD) acute myeloid leukemia (AML) in first complete remission (CR1) and who are randomized to receive gilteritinib or placebo beginning after completion of induction/consolidation chemotherapy for a two-year period.

Condition Intervention Phase
Acute Myeloid Leukemia (AML) Acute Myeloid Leukemia With FMS-like Tyrosine Kinase (FLT3) / Internal Tandem Duplication (ITD) Mutation Drug: gilteritinib Drug: Placebo Phase 3

Access to an investigational treatment associated with this study is available outside the clinical trial.   More info ...

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3 Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of the FLT3 Inhibitor Gilteritinib (ASP2215) Administered as Maintenance Therapy Following Induction/Consolidation Therapy for Subjects With FLT3/ITD AML in First Complete Remission

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. ):

Primary Outcome Measures:
  • Relapse-free Survival (RFS) [ Time Frame: Up to 61 months ]
    RFS is defined as the time from the date of randomization until the date of documented relapse or death from any cause, whichever occurs first. Relapse after Complete Remission (CR) (including Complete Remission with incomplete Platelet recovery (CRp) and Complete Remission with incomplete hematologic recovery (CRi)), is defined as bone marrow blasts 5% or higher (not attributable to regenerating bone marrow), any circulating blasts, any extra-medullary blast foci as per Revised International Working Group (IWG) criteria. Relapse events will be adjudicated by an independent review committee and will be used in the efficacy assessments, unless specifically stated otherwise.


Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: Up to 61 months ]
    OS is defined as the time from the date of randomization until the date of death from any cause. For surviving subjects, non-events will be censored at the date of last known date alive.

  • Event-free survival (EFS) [ Time Frame: Up to 61 months ]
    EFS is defined as the time from the date of randomization until the date of documented relapse or discontinuation of the treatment, or initiation of other anti-leukemic treatment or death from any cause, whichever occurs first.

  • Minimal Residual Disease (MRD) [ Time Frame: Up to 61 months ]
    MRD will be measured from bone marrow samples. FLT3/ITD mutation ratio will be measured in relation to total FLT3. Changes in FLT3/ITD mutation ratio will be compared with baseline/screening samples.

  • Safety assessed by Adverse Events (AEs) [ Time Frame: Up to 61 months ]
  • Number of participants with abnormal laboratory values and/or adverse events related to treatment [ Time Frame: Up to 61 months ]
  • Number of participants with abnormal vital signs and/or adverse events related to treatment [ Time Frame: Up to 61 months ]
  • Safety assessed by electrocardiograms (ECGs) [ Time Frame: Up to 61 months ]
    The 12-lead ECGs will be recorded in triplicate (3 separate ECGs, 10 minutes resting prior to first ECG and at least 5 minutes apart per time point) and transmitted electronically for central reading. The mean of the triplicate ECG from central read should be used for all final treatment decisions and AE reporting.

  • Number of participants with physical exam abnormalities and/or adverse events related to treatment [ Time Frame: Up to 61 months ]
  • Eastern Cooperative Oncology Group (ECOG) performance status score [ Time Frame: Up to 24 months ]
    ECOG performance status measured on 6 point scale to assess participant's performance status. 0=Fully active, able to carry on all pre-disease activities without restriction; 1=Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature; 2= Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours; 3=Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4=Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair; 5=Dead.


Estimated Enrollment: 354
Actual Study Start Date: January 10, 2017
Estimated Study Completion Date: March 2024
Estimated Primary Completion Date: March 2024 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ASP2215
Subjects will be treated with ASP2215 once daily (continuously for up to 2 years).
Drug: gilteritinib
Tablet to be taken orally once daily.
Other Name: ASP2215
Placebo Comparator: Placebo
Subjects will be treated with matching placebo tablets once daily (continuously for up to 2 years).
Drug: Placebo
Matching placebo tablet to be taken orally once daily.

Detailed Description:
Subjects in CR1 will be approached for this study after induction/consolidation therapy is complete and a decision not to proceed with transplantation is made or a suitable donor could not be identified. Subjects will be randomized in a 2:1 ratio to receive gilteritinib or placebo. Subjects will enter the screening period up to 14 days prior to the start of treatment. Subjects will be administered treatment over continuous 28-day cycles. After treatment discontinuation, subjects will have a 30-day follow-up visit for safety, after which the subjects will enter the long-term follow up period for collection of subsequent AML treatment, remission status, and survival (cause of death and date of death). Gilteritinib or placebo will be given daily for up to 2 years. Subjects will be followed for up to 3 years from the subjects 30-day follow up, or until 80% of the subjects have an RFS event, whichever comes first. Study drug will not be provided during the follow-up period.
  Eligibility

Information from the National Library of Medicine

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

Inclusion Criteria:

  • Subject is considered an adult according to local regulation at the time of obtaining consent form (ICF).
  • Subject consents to allow access to subject's diagnostic bone marrow aspirate or peripheral blood sample and/or the DNA derived from that sample, if available, that may be used to validate a companion diagnostic test that is being developed in parallel with gilteritinib.
  • Subject has confirmed morphologically documented AML, excluding acute promyelocytic leukemia (APL), in CR1 (including CRp and CRi). For the purposes of enrollment, CR will be defined as < 5% blasts in the bone marrow with no morphologic characteristics of acute leukemia (e.g., Auer rods) in the bone marrow with no evidence of extramedullary disease such as central nervous system involvement or granulocytic sarcoma.
  • Subject will not proceed with transplantation as either a decision not to proceed with transplantation has been made either on the recommendation of the treating physician or by the patient or a suitable donor could not be identified.
  • Subject is < 2 months from the start of the last cycle of consolidation and should have completed the recommended number of consolidations per local practice.
  • Subject has had no use of investigational agents, with the exception of FLT3 inhibiting agents during induction and/or consolidation therapy, within the prior 4 weeks.
  • Subject has had presence of the FLT3/ITD activating mutation in the bone marrow or peripheral blood as determined by the local institution at diagnosis.
  • Subject has an ECOG performance status 0 to 2.
  • Subject must meet the following criteria as indicated on the clinical laboratory tests:

    • Serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN), or if serum creatinine outside normal range, then glomerular filtration rate (GFR) > 40 mL/min/1.73m^2 as calculated with the 4-parameter Modification of Diet in Renal Disease (MDRD) equation.
    • Serum total bilirubin ≤ 2.5 mg/dL (43 μmol/L), except for subjects with Gilbert's syndrome.
    • Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x ULN.
    • Serum potassium and serum magnesium ≥ institutional lower limit of normal (LLN).
    • Absolute neutrophil count (ANC) ≥ 500/μl and platelets ≥ 20000/μl (unsupported by transfusions).
  • Subject is suitable for oral administration of study drug.
  • Female subject must either:

    • Be of nonchildbearing potential:
    • Postmenopausal (defined as at least 1 year without any menses) prior to screening, or
    • Documented surgically sterile or status posthysterectomy (at least 1 month prior to screening)
    • Or, if of childbearing potential,
    • Agree not to try to become pregnant during the study and for 6 months after the final study drug administration
    • And have a negative urine or serum pregnancy test at screening
    • And, if heterosexually active, agree to consistently use highly effective contraception per locally accepted standards (in addition to a barrier method) starting at screening and throughout the study period and for 6 months after the final study drug administration.
  • Female subject must agree not to breastfeed starting at screening and throughout the study period, and for 2 months and 1 week after the final study drug administration.
  • Female subject must not donate ova starting at screening and throughout the study period, and for 6 months after the final study drug administration.
  • Male subject and subject's female partners who are of childbearing potential must be using highly effective contraception per locally accepted standards (in addition to a barrier method) starting at screening and continue throughout the study period and for 4 months and 1 week after the final study drug administration.
  • Male subject must not donate sperm starting at screening and throughout the study period and for 4 months and 1 week after the final study drug administration.
  • Subject agrees not to participate in another interventional study while on treatment.

Exclusion Criteria:

  • Subject has had prior allogeneic transplant.
  • Subject has QTcF interval > 450 msec (average of triplicate determinations based on central reading).
  • Subject with Long QT Syndrome.
  • Subject with hypokalemia and hypomagnesemia at screening (defined as values below LLN).
  • Subject has clinically active central nervous system leukemia.
  • Subject is known to have human immunodeficiency virus infection.
  • Subject has active hepatitis B or C.
  • Subject has an uncontrolled infection. If a bacterial or viral infection is present, the subject must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to randomization. If a fungal infection is present, the subject must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection for 1 week prior to randomization.
  • Subject has progressing infection defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
  • Subject has uncontrolled angina, severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia, congestive heart failure New York Heart Association (NYHA) class 3 or 4 or subject has a history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or multigated acquisition (MUGA) scan performed within 1 month prior to study entry results in a left ventricular ejection fraction that is ≥ 45%.
  • Subject requires treatment with concomitant drugs that are strong inducers of cytochrome P450 (CYP) 3A.
  • Subject requires treatment with concomitant drugs that are strong inhibitors or inducers of P-glycoprotein (P-gp) with the exception of drugs that are considered absolutely essential for the care of the subject.
  • Subject requires treatment with concomitant drugs that target serotonin 5-hydroxytryptamine receptor 1 (5HT1R) or 5-hydroxytryptamine receptor 2B (5HT2BR) or sigma nonspecific receptor with the exception of drugs that are considered absolutely essential for the care of the subject.
  • Subject has a serious medical or psychiatric illness likely to interfere with participation in this clinical study.
  • Subject has prior malignancies, except resected basal cell carcinoma or treated cervical carcinoma in situ. Cancer treated with curative intent ≥ 5 years previously will be allowed. Cancer treated with curative intent < 5 years previously will not be allowed.
  • Subject has any condition which makes the subject unsuitable for study participation.
  Contacts and Locations
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): NCT02927262


Contacts
Contact: Astellas Pharma Global Development 800-888-7704 ext 5473 astellas.registration@astellas.com

  Show 154 Study Locations
Sponsors and Collaborators
Astellas Pharma Global Development, Inc.
Investigators
Study Director: Executive Medical Director Astellas Pharma Global Development, Inc.
  More Information

Responsible Party: Astellas Pharma Global Development, Inc.
ClinicalTrials.gov Identifier: NCT02927262     History of Changes
Other Study ID Numbers: 2215-CL-0302
2016-001643-39 ( EudraCT Number )
First Submitted: October 5, 2016
First Posted: October 7, 2016
Last Update Posted: December 1, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. ):
Acute myeloid leukemia
First Complete Remission
gilteritinib
FLT3/ITD
AML
ASP2215

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