Dose Escalation Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics of ASP2215 in Patients With Relapsed or Refractory Acute Myeloid Leukemia
NCT ID: NCT02014558
Last Updated: 2024-12-03
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE1/PHASE2
265 participants
INTERVENTIONAL
2013-10-09
2018-03-07
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Gilteritinib 20 mg in Escalation Phase
Participants received a single dose of 20 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Gilteritinib
Participants received gilteritinib oral tablets (10 mg, 40 mg or 100 mg, depending on the dose) once daily without food allowed for at least 2 hours before and 1 hour after dosing starting from day -2 and day of cycle 1, for continuous 28-day cycles.
Voriconazole
Participants received 200 mg voriconazole tablets daily every 12 hours starting from day 16 of cycle 1 through day 1 of cycle 2.
Gilteritinib 40 mg in Escalation Phase
Participants received a single dose of 40 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Gilteritinib
Participants received gilteritinib oral tablets (10 mg, 40 mg or 100 mg, depending on the dose) once daily without food allowed for at least 2 hours before and 1 hour after dosing starting from day -2 and day of cycle 1, for continuous 28-day cycles.
Gilteritinib 80 mg in Escalation Phase
Participants received a single dose of 80 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Gilteritinib
Participants received gilteritinib oral tablets (10 mg, 40 mg or 100 mg, depending on the dose) once daily without food allowed for at least 2 hours before and 1 hour after dosing starting from day -2 and day of cycle 1, for continuous 28-day cycles.
Gilteritinib 120 mg in Escalation Phase
Participants received a single dose of 120 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Gilteritinib
Participants received gilteritinib oral tablets (10 mg, 40 mg or 100 mg, depending on the dose) once daily without food allowed for at least 2 hours before and 1 hour after dosing starting from day -2 and day of cycle 1, for continuous 28-day cycles.
Gilteritinib 200 mg in Escalation Phase
Participants received a single dose of 200 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Gilteritinib
Participants received gilteritinib oral tablets (10 mg, 40 mg or 100 mg, depending on the dose) once daily without food allowed for at least 2 hours before and 1 hour after dosing starting from day -2 and day of cycle 1, for continuous 28-day cycles.
Gilteritinib 300 mg in Escalation Phase
Participants received a single dose of 300 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Gilteritinib
Participants received gilteritinib oral tablets (10 mg, 40 mg or 100 mg, depending on the dose) once daily without food allowed for at least 2 hours before and 1 hour after dosing starting from day -2 and day of cycle 1, for continuous 28-day cycles.
Gilteritinib 450 mg in Escalation Phase
Participants received a single dose of 450 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.
Gilteritinib
Participants received gilteritinib oral tablets (10 mg, 40 mg or 100 mg, depending on the dose) once daily without food allowed for at least 2 hours before and 1 hour after dosing starting from day -2 and day of cycle 1, for continuous 28-day cycles.
Gilteritinib 20 mg in Expansion Phase
Participants received 20 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. Starting on day 16 of cycle 1, participants also received 200 mg voriconazole orally every 12 hours through day 1 of cycle 2.
Gilteritinib
Participants received gilteritinib oral tablets (10 mg, 40 mg or 100 mg, depending on the dose) once daily without food allowed for at least 2 hours before and 1 hour after dosing starting from day -2 and day of cycle 1, for continuous 28-day cycles.
Gilteritinib 40 mg in Expansion Phase
Participants received 40 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study.
Gilteritinib
Participants received gilteritinib oral tablets (10 mg, 40 mg or 100 mg, depending on the dose) once daily without food allowed for at least 2 hours before and 1 hour after dosing starting from day -2 and day of cycle 1, for continuous 28-day cycles.
Gilteritinib 80 mg in Expansion Phase
Participants received 80 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study.
Gilteritinib
Participants received gilteritinib oral tablets (10 mg, 40 mg or 100 mg, depending on the dose) once daily without food allowed for at least 2 hours before and 1 hour after dosing starting from day -2 and day of cycle 1, for continuous 28-day cycles.
Gilteritinib 120 mg in Expansion Phase
Participants received 120 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study.
Gilteritinib
Participants received gilteritinib oral tablets (10 mg, 40 mg or 100 mg, depending on the dose) once daily without food allowed for at least 2 hours before and 1 hour after dosing starting from day -2 and day of cycle 1, for continuous 28-day cycles.
Gilteritinib 200 mg in Expansion Phase
Participants received 200 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, certain participants also received 500 mg cephalexin as a single oral dose.
Gilteritinib
Participants received gilteritinib oral tablets (10 mg, 40 mg or 100 mg, depending on the dose) once daily without food allowed for at least 2 hours before and 1 hour after dosing starting from day -2 and day of cycle 1, for continuous 28-day cycles.
Cephalexin
Participants received a single oral dose of 500 mg cephalexin tablet or capsule on day -1 and day 15 of cycle 1.
Gilteritinib 300 mg in Expansion Phase
Participants received 300 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, participants also received 2 mg midazolam as a single oral dose.
Gilteritinib
Participants received gilteritinib oral tablets (10 mg, 40 mg or 100 mg, depending on the dose) once daily without food allowed for at least 2 hours before and 1 hour after dosing starting from day -2 and day of cycle 1, for continuous 28-day cycles.
Midazolam
Participants received a single oral dose of 2 mg of midazolam syrup on day -1 and day 15 of cycle 1.
Interventions
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Gilteritinib
Participants received gilteritinib oral tablets (10 mg, 40 mg or 100 mg, depending on the dose) once daily without food allowed for at least 2 hours before and 1 hour after dosing starting from day -2 and day of cycle 1, for continuous 28-day cycles.
Voriconazole
Participants received 200 mg voriconazole tablets daily every 12 hours starting from day 16 of cycle 1 through day 1 of cycle 2.
Midazolam
Participants received a single oral dose of 2 mg of midazolam syrup on day -1 and day 15 of cycle 1.
Cephalexin
Participants received a single oral dose of 500 mg cephalexin tablet or capsule on day -1 and day 15 of cycle 1.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Refractory to at least 1 cycle of induction chemotherapy
* Relapsed after achieving remission with a prior therapy
* Subject has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
* Subject's interval from prior treatment to time of study drug administration is at least 2 weeks for cytotoxic agents (except hydroxyurea given for controlling blast cells), or at least 5 half-lives for prior experimental agents or noncytotoxic agents.
* Subject must meet the following criteria as indicated on the clinical laboratory tests\*:
* Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<2.5 x institutional upper limit normal (ULN)
* Total serum bilirubin \< 1.5x institutional ULN
* Serum creatinine \< 1.5 x institutional ULN or an estimated glomerular filtration rate (eGFR) of \> 50 ml/min as calculated by the Modification of Diet in Renal Disease (MDRD) equation.
* Subject agrees not to participate in another interventional study while on treatment.
Exclusion Criteria
* Subject has BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis).
* Subject has active malignant tumors other than AML or Myelodysplastic syndrome (MDS).
* Subject has persistent nonhematological toxicities of \>= Grade 2 (Common Terminology Criteria for Adverse Events v4), with symptoms and objective findings, from prior AML treatment (including chemotherapy, kinase inhibitors, immunotherapy, experimental agents, radiation, or surgery).
* Subject has had hematopoietic stem cell transplant (HSCT) and meets any of the following:
* Is within 2 months of transplant from C1D1
* Has clinically significant graft-versus-host disease requiring treatment
* Has \>= Grade 2 persistent non-hematological toxicity related to the transplant. Donor lymphocytes infusion (DLI) is not permitted \<= 30 days prior to study registration or during the first cycle of treatment on the study in Cohort 1 and first two cycles of the treatment in Cohort 2
* Subject has clinically active central nervous system leukemia
* Subject has disseminated intravascular coagulation abnormality (DIC)
* Subject has had major surgery within 4 weeks prior to the first study dose.
* Subject has had radiation therapy within 4 weeks prior to the first study dose
* Subject has congestive heart failure New York Heart Association (NYHA) class 3 or 4, or subject with a history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram performed within 3 months prior to study entry results in a left ventricular ejection fraction that is ≥ 45%
* Subject requires treatment with concomitant drugs that are strong inhibitors or inducers of Cytochrome P450-isozyme3A4 (CYP3A4) with the exception of antibiotics, antifungals, and antivirals that are used as standard of care post-transplant or to prevent or treat infections and other such drugs that are considered absolutely essential for the care of the subject
* Subject required treatment with concomitant drugs that target serotonin 5HT1R or 5HT2BR receptors or sigma nonspecific receptor with the exception of drugs that are considered absolutely essential for the care of the subject.
* Subject has an active uncontrolled infection
* Subject is known to have human immunodeficiency virus infection
* Subject has active hepatitis B or C, or other active hepatic disorder
18 Years
ALL
No
Sponsors
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Astellas Pharma Global Development, Inc.
INDUSTRY
Responsible Party
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Principal Investigators
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Executive Medical Director
Role: STUDY_DIRECTOR
Astellas Pharma Global Development
Locations
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Site US10021
Birmingham, Alabama, United States
Site US10023
Scottsdale, Arizona, United States
Site US10022
Duarte, California, United States
Site US10008
Los Angeles, California, United States
Site US10005
San Francisco, California, United States
Site US10001
Chicago, Illinois, United States
Site US10015
Chicago, Illinois, United States
Site US10012
Baltimore, Maryland, United States
Site US10003
Baltimore, Maryland, United States
Site US10006
Minneapolis, Minnesota, United States
Site US10011
Rochester, Minnesota, United States
Site US10020
Hackensack, New Jersey, United States
Site US10010
Buffalo, New York, United States
Site US10009
New York, New York, United States
Site US10013
New York, New York, United States
Site US10019
New York, New York, United States
Site US10014
Cleveland, Ohio, United States
Site US10018
Hershey, Pennsylvania, United States
Site US10004
Philadelphia, Pennsylvania, United States
Site US10017
Charleston, South Carolina, United States
Site US10007
Nashville, Tennessee, United States
Site US10002
Houston, Texas, United States
Site US10026
Fairfax, Virginia, United States
Site DE49002
Berlin, , Germany
Site DE49004
Dresden, , Germany
Site IT39001
Bologna, , Italy
Countries
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References
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James AJ, Smith CC, Litzow M, Perl AE, Altman JK, Shepard D, Kadokura T, Souda K, Patton M, Lu Z, Liu C, Moy S, Levis MJ, Bahceci E. Pharmacokinetic Profile of Gilteritinib: A Novel FLT-3 Tyrosine Kinase Inhibitor. Clin Pharmacokinet. 2020 Oct;59(10):1273-1290. doi: 10.1007/s40262-020-00888-w.
Perl AE, Altman JK, Cortes J, Smith C, Litzow M, Baer MR, Claxton D, Erba HP, Gill S, Goldberg S, Jurcic JG, Larson RA, Liu C, Ritchie E, Schiller G, Spira AI, Strickland SA, Tibes R, Ustun C, Wang ES, Stuart R, Rollig C, Neubauer A, Martinelli G, Bahceci E, Levis M. Selective inhibition of FLT3 by gilteritinib in relapsed or refractory acute myeloid leukaemia: a multicentre, first-in-human, open-label, phase 1-2 study. Lancet Oncol. 2017 Aug;18(8):1061-1075. doi: 10.1016/S1470-2045(17)30416-3. Epub 2017 Jun 20.
Kasi PM, Litzow MR, Patnaik MM, Hashmi SK, Gangat N. Clonal evolution of AML on novel FMS-like tyrosine kinase-3 (FLT3) inhibitor therapy with evolving actionable targets. Leuk Res Rep. 2016 Jan 12;5:7-10. doi: 10.1016/j.lrr.2016.01.002. eCollection 2016.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Related Links
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Link to results on the Astellas Clinical Study Results website
Other Identifiers
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2215-CL-0101
Identifier Type: -
Identifier Source: org_study_id