Clinical Trial - NCT02997202

       

A Trial of the FMS-like Tyrosine Kinase 3 (FLT3) Inhibitor Gilteritinib Administered as Maintenance Therapy Following Allogeneic Transplant for Patients With FLT3/Internal Tandem Duplication (ITD) Acute Myeloid Leukemia (AML)

Active, not recruiting

Sponsor: Astellas Pharma Global Development, Inc.

Collaborators: National Heart, Lung, and Blood Institute (NHLBI), Blood and Marrow Transplant Clinical Trials Network

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT02997202

Protocol Info

Short Description: Phase III of Gilteritinib as Maintenance Therapy Following Allo Transplant for FLT3/ITD AML
Long Description: A Multi-center, Randomized, Double-blind, Placebo-controlled Phase III Trial of the FLT3 Inhibitor Gilteritinib Administered as Maintenance Therapy Following Allogeneic Transplant for Patients with FLT3/ITD AML
MGH Status: Closed
Sponsor: BMT CTN
Disease Program: BMT

Next Steps


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Purpose

The purpose of this study is to compare relapse-free survival between participants with FLT3/ITD AML in first morphologic complete remission (CR1) who undergo hematopoietic stem cell transplant (HCT) and are randomized to receive gilteritinib or placebo beginning after the time of engraftment for a two year period.
Condition Title Intervention Phase
Acute Myeloid Leukemia gilteritinib Placebo Phase 3
Study Type Interventional
Official Title A Multi-center, Randomized, Double-blind, Placebo-controlled Phase III Trial of the FLT3 Inhibitor Gilteritinib Administered as Maintenance Therapy Following Allogeneic Transplant for Patients With FLT3/ITD AML

Primary Outcome Measures

Relapse-free survival [Time Frame: 84 months] [Designated as safety issue: ]


Secondary Outcome Measures

Safety and tolerability assessed by incidence and severity of adverse events [Time Frame: 24 months] [Designated as safety issue: ]

Overall Survival (OS) [Time Frame: 84 months] [Designated as safety issue: ]

Non-relapse Mortality [Time Frame: 84 months] [Designated as safety issue: ]

Event-free Survival (EFS) at 12 months [Time Frame: 12 months] [Designated as safety issue: ]

Event-free Survival (EFS) at 24 months [Time Frame: 24 months] [Designated as safety issue: ]

Cumulative Incidence of Acute Graft vs. Host Disease (GVHD) [Time Frame: 6 months] [Designated as safety issue: ]

Cumulative Incidence of Chronic GVHD at 12 months [Time Frame: 12 months] [Designated as safety issue: ]

Cumulative Incidence of Chronic GVHD at 24 months [Time Frame: 24 months] [Designated as safety issue: ]

The cumulative incidence of detection of FLT3/ITD MRD [Time Frame: 24 months] [Designated as safety issue: ]

Incidence of Severity of Infection [Time Frame: 28 months] [Designated as safety issue: ]

Estimated Enrollment: 356
Study Start Date: June 2017
Estimated Study Completion Date: April 2025
Estimated Primary Completion Date: April 2025
Arms Assigned Interventions

Experimental:Gilteritinib

Participants will take gilteritinib once daily for continuous daily dosing.
Drug:gilteritinib
oral

Placebo Comparator:Placebo

Participants will take placebo once daily for continuous daily dosing.
Drug:Placebo
oral

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

Registration Inclusion Criteria

  • • Participant is considered a suitable candidate for HCT and has an acceptable source of allogeneic donor stem cells, as defined per institutional practice (allogeneic HCT for any donor source [matched sibling, unrelated donor (URD), mismatched URD, related haploidentical, or umbilical cord blood] and any graft source [umbilical cord, BM, peripheral blood (PB)], and any conditioning [myeloablative conditioning (MAC), reduced intensity conditioning (RIC), or non-myeloablative conditioning (NMA)] will be permitted).
  • • Participant is considered a legal adult by local regulation at the time of signing informed consent form (ICF).
  • • Participant consents to allow access to diagnostic BM aspirate or PB sample and/or the DNA derived from that sample, if available, that may be used to validate a companion diagnostic that is being developed in parallel with gilteritinib.
  • • Participant has confirmed, morphologically documented AML in CR1. For the purposes of registration, CR1 will be defined as < 5% blasts in the BM with no morphologic characteristics of acute leukemia (e.g., Auer Rods) in the BM with no evidence of extramedullary disease such as central nervous system involvement or granulocytic sarcoma.
  • • Participant has not received more than 2 cycles of induction chemotherapy to achieve CR1. The induction cycles can be the same regimen or different regimens. The regimen(s) may contain conventional agents, investigational agents, or a combination of both.
  • • Participants with CR with incomplete count recovery (CRp or CRi) are allowed. Incomplete platelet recovery (CRp) is defined as CR with platelet count < 100 x 109/L. Incomplete blood count recovery (CRi) is defined as CR with residual neutropenia < 1 x 109/L with or without complete platelet recovery. Red blood cell count (RBC) and platelet transfusion independence is not required.
  • • The maximum time allowed from establishment of CR1 to registration is 12 months.
  • • Participant has presence of the FLT3/ITD activating mutation in the BM or PB as determined by the local institution at diagnosis.
  • • Participant must meet the following criteria as indicated on the clinical laboratory tests:
  • • Serum creatinine within normal range, or if serum creatinine outside normal range, then glomerular filtration rate (GFR) > 40 mL/min/1.73m2 as calculated with the Cockcroft-Gault equation with adjustment if total body weight is = 125% of ideal body weight.
  • • Total bilirubin (TBL) = 2.5 mg/dL, except for participants with Gilbert's syndrome.
  • • Serum AST and/or alanine aminotransferase (ALT) < 3 x institutional upper limit of normal (ULN).
  • • Participant has left ventricular ejection fraction at rest = 40%.
  • • Participant has diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin) = 50% predicted and/or forced expiratory volume in 1 second (FEV1) = 50% predicted.
  • • Female participants must either:
  • • Be of non-childbearing potential:
  • • postmenopausal (defined as at least 1 year without menses) prior to screening or
  • • documented as surgically sterilized (at least 1 month prior to the screening visit)
  • • Or, if of childbearing potential,
  • • Agree not to try to become pregnant during the study for 6 months after the final study drug administration
  • • And have a negative 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.
  • • For United Kingdom sites:
  • • Highly effective forms of birth control include:
  • • Consistent and correct usage of established hormonal contraceptives that inhibit ovulation
  • • Established intrauterine device (IUD) or intrauterine system (IUS)
  • • Female participants must agree not to breastfeed or donate ova throughout the study drug treatment period and for 6 months after the final study drug administration.
  • • Male participants (even if surgically sterilized), and partners who are women of childbearing potential must be using highly effective contraception in addition to a barrier method throughout the study drug treatment period and for 127 days after the final study drug administration.
  • • For United Kingdom sites:
  • • Highly effective forms of birth control include:
  • • Consistent and correct usage of established hormonal contraceptives that inhibit ovulation
  • • Established IUD or IUS
  • • Vasectomy (A vasectomy is a highly effective contraception method provided the absence of sperm has been confirmed. If not, an additional highly effective method of contraception should be used.)
  • • Male is sterile due to a bilateral orchiectomy
  • • Male participants must not donate sperm throughout the study drug treatment period and for 127 days after the final study drug administration.
  • • Participant is able to take an oral medication.
  • • Participant agrees not to participate in another interventional study while on treatment.

Randomization Inclusion Criteria

  • • Participant is = 30 days and = 90 days from hematopoietic cell infusion.
  • • Participant has achieved engraftment. Engraftment is defined as ANC = 500 cells/µL and platelets = 20000/µL on 3 consecutive measurements (each occurring at least 1 day apart). The participant must not have had a platelet transfusion within 7 days prior to the first measurement.
  • • Participant has confirmed ongoing morphologically documented AML in CR1. For the purposes of randomization, CR1 will be defined as < 5% blasts with no morphologic characteristics of acute leukemia (e.g., Auer Rods) in the BM with no evidence of extramedullary disease such as central nervous system involvement or granulocytic sarcoma.
  • • Participant meets the following criteria as indicated on the clinical laboratory tests:
  • • Serum creatinine within normal range, or if serum creatinine outside normal range, then GFR > 40 mL/min/1.73m2 as calculated with the Cockcroft-Gault equation with adjustment if total body weight is = 125% of ideal body weight.
  • • TBL < 2.5 mg/dL, except for participants with Gilbert's syndrome.
  • • Serum AST and/or ALT < 3 x institutional ULN.
  • • Serum potassium and magnesium = the institutional lower limit of normal (LLN).
  • • If the participant has developed overall grades II-IV acute GVHD, the following criteria must be met to be randomized:
  • • No requirement of > 0.5 mg/kg of prednisone (or equivalent) daily dose within 1 week of randomization
  • • No escalation of systemic immunosuppression in terms of increase of corticosteroids or addition of new agent / modality within 2 weeks of randomization. (Note that increasing calcineurin inhibitors or sirolimus to achieve therapeutic trough levels is allowed.) Topical skin and topical gastrointestinal steroids are allowed.
  • • Participant is able to take oral medication.

Registration Exclusion Criteria

  • • Participant has had a prior allogeneic transplant.
  • • Participant has Karnofsky performance status score < 70% .
  • • Participant requires treatment with concomitant drugs that are strong inducers of CYP3A within 14 days of start of study drug.
  • • Participant 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 participant.
  • • Participant has a Fridericia-corrected QT interval (QTcF) > 450 msec (average of triplicate determinations) per central read.
  • • Participant has long QT Syndrome at screening.
  • • Participant has a known infection with human immunodeficiency virus (HIV).
  • • Participant has active hepatitis B infection as determined by NAAT or surface antigen assay. Participants who have acquired immunity from past exposure (HBcAb positive / HBsAb positive / HBsAg negative) are eligible.
  • • Participant has active hepatitis C infection as determined by NAAT. NAAT must be performed if the participant has positive serology for hepatitis C. Participants who have had past exposure and have no detectable virus either through spontaneous clearance or treatment are eligible.
  • • Participant has an uncontrolled infection. If a bacterial or viral infection is present, the participant must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to registration. If a fungal infection is present, the participant must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection for 1 week prior to registration.
  • • Progressing infection is 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.
  • • Participant has had a myocardial infarction within 6 months prior to registration or New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia.
  • • Participant has a serious medical or psychiatric illness likely to interfere with participation in this clinical study.
  • • Participant is breast feeding or pregnant.
  • • Participant has prior malignancies, except lobular breast carcinoma in situ, fully resected basal cell or squamous cell carcinoma of skin 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.

Randomization Exclusion Criteria

  • • Participant requires treatment with concomitant drugs that are strong inducers of CYP3A within 14 days of starting study drug.
  • • Participant requires treatment with concomitant drugs that target serotonin 5HT1R or 5HT2BR or sigma nonspecific receptor with the exception of drugs that are considered by the investigator to be absolutely essential for the care of the participant and for which no acceptable alternative exists.
  • • Participant has a QTcF interval > 450 msec (average of triplicate determinations) by central read.
  • • Participant has a need for supplemental oxygen with the exception of using previously existing non-invasive continuous positive airway pressure (CPAP) at night.
  • • Participant has used investigational agents within 4 weeks of randomization.
  • • Participant has used experimental therapy for acute GVHD within 4 weeks of randomization. If unsure of the definition of "experimental", discussion with one of the protocol chairs is recommended.
  • • Participant has an uncontrolled infection. If a bacterial or viral infection is present, the participant 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 participant must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection for 1 week prior to randomization.
  • • Progressing infection is 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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT02997202

Locations

  • United States, Alabama
    • University of Alabama at Birmingham Birmingham, Alabama, United States, 35294
  • United States, Arizona
    • Mayo Clinic Phoenix, Arizona, United States, 85054
    • Virginia G Piper Cancer Center Scottsdale, Arizona, United States, 85258
  • United States, California
    • University of California San Francisco San Francisco, California, United States, 94143
    • Stanford University Stanford, California, United States, 94305
  • United States, Connecticut
    • Yale University School of Medicine New Haven, Connecticut, United States, 06511
  • United States, Florida
    • University of Florida Gainesville, Florida, United States, 32610
    • University of Miami Miami, Florida, United States, 33136
    • H. Lee Moffitt Cancer Center Tampa, Florida, United States, 33612
  • United States, Georgia
    • Emory University Atlanta, Georgia, United States, 30322
    • Northside Atlanta, Georgia, United States, 30342
    • Augusta University Augusta, Georgia, United States, 30912
  • United States, Illinois
    • Northwestern Memorial Hospital Chicago, Illinois, United States, 60611
    • Rush University Medical Center Chicago, Illinois, United States, 60612
    • Loyola University Medical Center Maywood, Illinois, United States, 60153
  • United States, Indiana
    • Indiana Blood and Marrow Transplant Indianapolis, Indiana, United States, 46237
  • United States, Kansas
    • University of Kansas Medical Center Kansas City, Kansas, United States, 66160-7233
  • United States, Maryland
    • University of Maryland Medical Systems Baltimore, Maryland, United States, 21201
    • Johns Hopkins Hospital Baltimore, Maryland, United States, 21231
  • United States, Massachusetts
    • Tufts Medical Center Boston, Massachusetts, United States, 02111
    • Massachusetts General Hospital Boston, Massachusetts, United States, 02114
    • Beth Israel Deaconess Medical Center Boston, Massachusetts, United States, 02215
    • Dana Farber Cancer Institute Boston, Massachusetts, United States, 02215
    • University of Massachusetts Worcester, Massachusetts, United States, 01655
  • United States, Michigan
    • Karmanos Cancer Center Detroit, Michigan, United States, 48201
  • United States, Minnesota
    • University of Minnesota School of Medicine Minneapolis, Minnesota, United States, 55455
    • Mayo Clinic Rochester, Minnesota, United States, 55905
  • United States, Missouri
    • Washington University in St. Louis Saint Louis, Missouri, United States, 63110
  • United States, Nebraska
    • University of Nebraska Medical Center Omaha, Nebraska, United States, 68198
  • United States, New York
    • Memorial Sloan Kettering New York, New York, United States, 10065
    • Weill Cornell Medical Center New York, New York, United States, 10065
  • United States, North Carolina
    • University of North Carolina Chapel Hill, North Carolina, United States, 27599
    • Duke University Medical Center Durham, North Carolina, United States, 27710
    • Wake Forest Baptist Health Winston-Salem, North Carolina, United States, 27157
  • United States, Ohio
    • Oncology Hematology Care, Inc Cincinnati, Ohio, United States, 45242
    • University Hospitals of Cleveland Medical Center Cleveland, Ohio, United States, 44106
    • Cleveland Clinic Cleveland, Ohio, United States, 44195
    • Ohio State University, The Columbus, Ohio, United States, 43210
  • United States, Oregon
    • Oregon Health and Science University Portland, Oregon, United States, 97239
  • United States, Pennsylvania
    • University of Pennsylvania Philadelphia, Pennsylvania, United States, 19104
  • United States, Tennessee
    • Vanderbilt University Medical Center Nashville, Tennessee, United States, 37232
  • United States, Texas
    • Baylor College of Medicine Houston, Texas, United States, 77030
  • United States, Utah
    • Huntsman Cancer Institute Salt Lake City, Utah, United States, 84132
    • Intermountain BMT Salt Lake City, Utah, United States, 84143
  • United States, Virginia
    • University of Virginia Charlottesville, Virginia, United States, 22908
    • Virginia Commonwealth University Richmond, Virginia, United States, 23298
  • United States, Washington
    • Fred Hutchinson Cancer Research Center Seattle, Washington, United States, 98109
  • United States, West Virginia
    • West Virginia University Hospital Morgantown, West Virginia, United States, 26506-9214
  • United States, Wisconsin
    • University of Wisconsin Hospital and Clinics Madison, Wisconsin, United States, 53792
    • Medical College of Wisconsin Milwaukee, Wisconsin, United States, 53226
  • Australia,
    • Site AU61001 Liverpool, , Australia,
    • Site AU61002 Melbourne, , Australia,
    • Site AU61004 Westmead, , Australia,
  • Belgium,
    • Site BE32003 Bruxelles, , Belgium,
    • Site BE32004 Gent, , Belgium,
    • Site BE32001 Liege, , Belgium,
  • Canada,
    • Site CA15004 Hamilton, , Canada,
    • Site CA15003 Montreal, , Canada,
    • Site CA15002 Winnipeg, , Canada,
  • Denmark,
    • Site DK45002 Arhus, , Denmark,
    • Site DK45001 Copenhagen, , Denmark,
  • France,
    • Site FR33012 Besancon, , France,
    • Site FR33007 Lille, , France,
    • Site FR33004 Lyon, , France,
    • Site FR33009 Marseille, , France,
    • Site FR33005 Paris, , France,
    • Site FR33008 Pessac, , France,
    • Site FR33010 Vandoeuvre-Les-Nancy, , France,
  • Germany,
    • Site DE49002 Düsseldorf, , Germany,
    • Site DE49003 Halle (Saale), , Germany,
    • Site DE49005 Hamburg, , Germany,
    • Site DE49006 Köln, , Germany,
    • Site DE49007 Mainz, , Germany,
    • Site DE49004 Münster, , Germany,
  • Greece,
    • Site GR30004 Athens, , Greece,
    • Site GR30003 Rio, , Greece,
    • Site GR30001 Thessaloniki, , Greece,
  • Italy,
    • Site IT39005 Bergamo, , Italy,
    • Site IT39006 Bologna, , Italy,
    • Site IT39009 Genova, , Italy, 16132
    • Site IT39002 Milano, , Italy,
    • Site IT39007 Milano, , Italy,
    • Site IT39011 Pescara, , Italy,
    • Site IT39003 Roma, , Italy,
    • Site IT39001 Torino, , Italy,
    • Site IT39004 Udine, , Italy,
  • Japan, Aichi
    • Site JP81014 Anjo, Aichi, Japan,
    • Site JP81011 Nagoya, Aichi, Japan,
  • Japan, Hokkaido
    • Site JP81018 Sapporo, Hokkaido, Japan,
  • Japan, Hyogo
    • Site JP81021 Kobe, Hyogo, Japan,
    • Site JP81012 Nishinomiya, Hyogo, Japan,
  • Japan, Kanagawa
    • Site JP81002 Isehara, Kanagawa, Japan,
    • Site JP81007 Yokohama, Kanagawa, Japan,
  • Japan, Miyagi
    • Site JP81010 Sendai, Miyagi, Japan,
  • Japan, Osaka
    • Site JP81006 Suita, Osaka, Japan,
  • Japan, Tochigi
    • Site JP81008 Shimotsuke, Tochigi, Japan,
  • Japan, Tokyo
    • Site JP81013 Bunkyo-ku, Tokyo, Japan,
    • Site JP81004 Chuo-ku, Tokyo, Japan,
    • Site JP81016 Minato-ku, Tokyo, Japan,
    • Site JP81020 Shinjuku-ku, Tokyo, Japan,
  • Japan,
    • Site JP81001 Fukuoka, , Japan,
    • Site JP81003 Fukuoka, , Japan,
    • Site JP81019 Kagoshima, , Japan,
    • Site JP81015 Kyoto, , Japan,
    • Site JP81017 Okayama, , Japan,
    • Site JP81005 Osaka, , Japan,
  • Korea, Republic of,
    • Site KR82001 Seoul, , Korea, Republic of,
    • Site KR82002 Seoul, , Korea, Republic of,
    • Site KR82003 Seoul, , Korea, Republic of,
    • Site KR82004 Seoul, , Korea, Republic of,
    • Site KR82005 Seoul, , Korea, Republic of,
  • New Zealand,
    • Site NZ64002 Christchurch, , New Zealand,
    • Site NZ64001 Grafton, , New Zealand, 1010
  • Poland,
    • Site PL48003 Krakow, , Poland,
    • Site PL48004 Warszawa, , Poland,
  • Spain,
    • Site ES34004 Barcelona, , Spain, 08036
    • Site ES34003 Barcelona, , Spain,
    • Site ES34005 Barcelona, , Spain,
    • Site ES34006 Salamanca, , Spain,
    • Site ES34007 Santander, , Spain,
    • Site ES34002 Valencia, , Spain,
  • Taiwan,
    • Site TW88603 Taichung, , Taiwan,
    • Site TW88602 Taipei, , Taiwan,
    • Site TW88605 Taoyuan, , Taiwan,
  • United Kingdom,
    • Site GB44010 Birmingham, , United Kingdom,
    • Site GB44003 Bristol, , United Kingdom,
    • Site GB44009 Glasgow, , United Kingdom, G12 0YN
    • Site GB44004 London, , United Kingdom,
    • Site GB44002 Manchester, , United Kingdom,
    • Site GB44005 Nottingham, , United Kingdom,
    • Site GB44001 Sutton, , United Kingdom,

Sponsors and Collaborators

Astellas Pharma Global Development, Inc.

National Heart, Lung, and Blood Institute (NHLBI)

Blood and Marrow Transplant Clinical Trials Network

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT02997202
Other Study ID Numbers: 2016-001061-83
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Astellas Pharma Inc:

Gilteritinib

ASP2215

Safety and Efficacy

Acute Myeloid Leukemia

Additional relevant MeSH terms:

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on January 20, 2021