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Dose Escalation Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics of ASP2215 in Patients With Relapsed or Refractory Acute Myeloid Leukemia

Primary Purpose

Acute Myeloid Leukemia

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Gilteritinib

Voriconazole

Midazolam

Cephalexin

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring Acute Myeloid Leukemia, Gilteritinib, ASP2215

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Subject is defined as morphologically documented primary or secondary AML by the World Health Organization (WHO) criteria (2008) and fulfills one of the following:
- 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 was diagnosed as acute promyelocytic leukemia (APL).
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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm Type

Experimental

Arm Label

Gilteritinib 20 mg in Escalation Phase

Gilteritinib 40 mg in Escalation Phase

Gilteritinib 80 mg in Escalation Phase

Gilteritinib 120 mg in Escalation Phase

Gilteritinib 200 mg in Escalation Phase

Gilteritinib 300 mg in Escalation Phase

Gilteritinib 450 mg in Escalation Phase

Gilteritinib 20 mg in Expansion Phase

Gilteritinib 40 mg in Expansion Phase

Gilteritinib 80 mg in Expansion Phase

Gilteritinib 120 mg in Expansion Phase

Gilteritinib 200 mg in Expansion Phase

Gilteritinib 300 mg in Expansion Phase

Arm Description

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Number of Participants With Dose Limiting Toxicities (DLTs)

To determine the maximum tolerated dose, safety was assessed by DLTs, defined as any grade ≥ 3 non-hematologic or extramedullary toxicity that occurred within 30 days starting with the first dose taken on day -2, and included the first treatment cycle in the dose escalation phase and in the first treatment cycle (28 days) in the dose expansion phase, that was considered to be possibly or probably related to study drug. Exceptions to this were the following: (1) Alopecia, anorexia or fatigue, (2) Grade 3 nausea and/or vomiting if not required tube feeding or total parenteral nutrition, or diarrhea if not required or prolonged hospitalization that was managed to grade ≤ 2 with standard antiemetic or antidiarrheal medications used at prescribed dose within 7 days of onset, (3) Grade 3 fever with neutropenia, with or without infection, (4) Grade 3 infection.

Number of Participants With Adverse Events (AEs)

Safety was assessed by AEs, which included abnormalities identified during a medical test (e.g. laboratory tests, vital signs, electrocardiogram, etc.) if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study medication or was clinically significant. A treatment-emergent AE (TEAE) was defined as an AE observed after starting administration of the study drug up to 30 days after last dose of study drug (for participants who underwent hematopoietic stem cell transplantation [HSCT]: defined as AEs observed after starting study drug until the last dose before on study HSCT plus 30 days, and AEs that began after resumption of gilteritinib and within 30 days after the last dose of gilteritinib). AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (1-Mild, 2-Moderate, 3-Severe, 4-LifeThreatening, 5-Death).

Area Under the Concentration-time Curve Over the 24-Hour Dosing Interval (AUC24) After Single and Multiple Doses of Gilteritinib

Plasma samples were used for pharmacokinetic assessments.

Maximum Concentration (Cmax) After Single and Multiple Doses of Gilteritinib

Plasma samples were used for pharmacokinetic assessments.

Area Under the Concentration-time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) After Single and Multiple Doses of Gilteritinib

Plasma samples were used for pharmacokinetic assessments.

Time to Observed Cmax (Tmax) After Single and Multiple Doses of Gilteritinib

Plasma samples were used for pharmacokinetic assessments.

Terminal Elimination Half-life (t1/2) After Multiple Doses of Gilteritinib

Plasma samples were used for pharmacokinetic assessments.

Accumulation Ratio After Multiple Doses of Gilteritinib

Plasma samples were used for pharmacokinetic assessments.

Secondary Outcome Measures

Percentage of Participants With Complete Remission (CR) During the First 2 Cycles

CR was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in CR when they had bone marrow regenerating normal hematopoietic cells, achieved a morphologic leukemia-free state, had an absolute neutrophil count (ANC) > 1 x 10^9/L, platelet count ≥ 100 x 10^9/L, normal marrow differential with < 5% blasts, had been red blood cell (RBC) and platelet transfusion independent (defined as 1 week without RBC transfusion and 1 week without platelet transfusion), had no presence of Auer rods and no evidence of extramedullary leukemia, and blast counts in peripheral blood had been ≤ 2%. Exact 95% confidence interval was estimated using binomial distribution.

Percentage of Participants With CR During Treatment

Percentage of Participants With CR With Incomplete Platelet Recovery (CRp)

CRp was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in CRp when they achieved CR except for incomplete platelet recovery (< 100 x 10^9/L). Exact 95% confidence interval was estimated using the binomial distribution.

Percentage of Participants With CR With Incomplete Hematological Recovery (CRi)

CRi was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in CRi when they fulfilled all the criteria for CR except for incomplete hematological recovery with residual neutropenia < 1 x 10^9/L with or without complete platelet recovery. RBC and platelet transfusion independence were not required. Exact 95% confidence interval was estimated using the binomial distribution.

Percentage of Participants With Complete Remission With Partial Hematologic Recovery (CRh)

CRh was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in CRh when they could not be classified as being in CR and had bone marrow blasts < 5% and partial hematologic recovery ANC >= 0.5 x 10^9/L and platelets >= 50 x 10^9/L. There should not be evidence of extramedullary leukemia. Exact 95% confidence interval was estimated using the binomial distribution. CRh was calculated only for participants who were FLT3 mutation positive.

Percentage of Participants With Composite CR (CRc)

CRc was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in CRc when they had achieved either CR, complete remission with incomplete platelet recovery (CRp, defined as had achieved CR except for incomplete platelet recovery (< 100 x 10^9/L) or complete remission with incomplete hematologic recovery (CRi, defined as had fulfilled all the criteria for CR except for incomplete hematological recovery with residual neutropenia < 1 x 10^9/L with or without complete platelet recovery; RBC platelet transfusion independence not required). Exact 95% confidence interval was estimated using the binomial distribution.

Percentage of Participants With Partial Remission (PR)

PR was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in PR when they had bone marrow regenerating normal hematopoietic cells with evidence of peripheral recovery with no (or only a few regenerating) circulating blasts and with a decrease of at least 50% in the percentage of blasts in the bone marrow aspirate with the total marrow blasts between 5% and 25%. A value of less or equal than 5% blasts was also considered a PR if Auer rods were present. There should be no evidence of extramedullary leukemia. Exact 95% confidence interval was estimated using the binomial distribution.

Percentage of Participants With Best Response

Best response was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). BR was defined as the best measured response for all visits (in the order of CR, CRp, CRi, and PR) post-treatment. Participants who achieved the best response of CR, CRp, CRi or PR were classified as responders. Participants who did not achieve at least PR were considered as non-responders. Exact 95% confidence interval was estimated using the binomial distribution.

Percentage of Participants With Complete Remission and Complete Remission With Partial Hematologic Recovery (CR/CRh)

Participants with CR/CRh were defined as participants who achieved either CR or CRh. Participants with CR had bone marrow regenerating normal hematopoietic cells, achieved a morphologic leukemia-free state, had an ANC > 1 x 10^9/L, platelet count ≥ 100 x 10^9/L, and normal marrow differential with < 5% blasts, had been RBC and platelet transfusion independent (defined as 1 week without RBC transfusion and 1 week without platelet transfusion). Also, there had been no presence of Auer rods, no evidence of extramedullary leukemia, and blast counts in peripheral blood had been ≤ 2%. Participants with CRh could not be classified as being in CR and had bone marrow blasts < 5%, partial hematologic recovery ANC >= 0.5 x 10^9/L and platelets >= 50 x 10^9/L. There should not be evidence of extramedullary leukemia. Exact 95% confidence interval was estimated using the binomial distribution. CR/CRh was calculated only for participants who were FLT3 mutation positive.

Duration of CR (DCR)

DCR was defined as the time from the date of first CR until the date of documented relapse for participants who achieved CR. Participants who died without report of relapse were considered non-events and censored at their last relapse-free disease assessment date. Other participants who did not relapse on study were considered non-events and censored at the last relapse-free disease assessment date. DCR was calculated using Kaplan-Meier method and therefore data are estimated.

Duration of CRp (DCRp)

DCRp was defined as the time from the date of first CRp until the date of documented relapse for participants who achieved CRp. Participants who died without report of relapse were considered non-events and censored at their last relapse-free disease assessment date. Other participants who did not relapse on study were considered non-events and censored at the last relapse-free disease assessment date. DCRp was calculated using Kaplan-Meier method and therefore data are estimated.

Duration of CRi (DCRi)

DCRi was defined as the time from the date of first CRi until the date of documented relapse for participants who achieved CRi. Participants who died without report of relapse and participants who did not relapse were considered non-events and censored at the last relapse-free disease assessment date. DCRi was calculated using Kaplan-Meier method and therefore data are estimated.

Duration of CRh (DCRh)

DCRh was defined as the time from the date of first CRh until the date of documented relapse for participants who achieved CRh but did not have a best response of CR. Participants who died without report of relapse and participants who did not relapse were considered non-events and censored at the last relapse-free disease assessment date. DCRh was calculated using Kaplan-Meier method and therefore data are estimated. DCRh was calculated only for participants who were FLT3 mutation positive.

Duration of CRc (DCRc)

DCRc was defined as the time from the date of first CRc until the date of documented relapse for participants who achieved CRc. Participants who died without report of relapse and participants who did not relapse were considered non-events and censored at the last relapse-free disease assessment date. DCRc was calculated using Kaplan-Meier method and therefore data are estimated.

Duration of CR/CRh (DCRCRh)

DCRCRh was defined as the time from the date of first DCRCRh until the date of documented relapse for participants who achieved CR or CRh. For participants who achieved both CR and CRh, the first CR date or CRh date, whichever occurred first, was used. Participants who died without report of relapse and participants who did not relapse were considered non-events and censored at the last relapse-free disease assessment date. DCRCRh was calculated using Kaplan-Meier method and therefore data are estimated. DCRCRh was calculated only for participants who were FLT3 mutation positive.

Duration of Response

Duration of response was defined as the time from the date of either first CRc or PR until the date of documented relapse of any type for participants who achieved CRc or PR. Participants who died without report of relapse were considered non-events and censored at their last relapse-free disease assessment date. Other participants who did not relapse on study are considered non-events and censored at the last relapse-free assessment date. Duration of response was calculated using Kaplan-Meier method and therefore data are estimated.

Time to CR (TTCR)

TTCR was defined as the time from the first dose of study drug until the date of first CR.

Time to CRp (TTCRp)

TTCRp was defined as the time from the first dose of study drug until the date of first CRp. TTCRp was evaluated for participants who achieved CRp.

Time to CRi (TTCRi)

TTCRi was defined as the time from the first dose of study drug until the date of first CRi. TTCRi was evaluated for participants who achieved CRi.

Time to First CR/CRh (TTFCRCRh)

TTFCRCRh was defined as the time from the first dose of study drug until the date of first either CR or CRh. TTFCRCRh was evaluated for participants who achieved CR or CRh. For participants who achieve both CR and CRh, the first CR date or CRh date, whichever occurs first was used. TTFCRCRh was calculated only for participants who were FLT3 mutation positive.

Time to Best CR/CRh (TTBCRCRh)

TTBCRCRh was defined as the time from the first dose of study drug until the first date that the best response of CR or CRh was achieved. TTBCRCRh was evaluated for participants who achieved CR or CRh. For participants who achieve both CR and CRh, the first CR date was used. TTBCRCRh was calculated only for participants who were FLT3 mutation positive.

Time to CRc (TTCRc)

TTCRc was defined as the time from the first dose of study drug until the date of first CRc. TTCRc was evaluated for participants who achieved CRc.

Time to Response (TTR)

TTR was defined as the time from the first dose of study drug until the date of either first CRc or PR. TTR was evaluated for participants who achieved CRc or PR.

Time to Best Response (TTBR)

TTBR was defined as the time from the first dose of study drug until the first disease assessment date when participant achieved best response. TTBR was evaluated in participants who achieved best response of CR, CRp, CRi, or PR.

Overall Survival (OS)

The time from the date of first dose of study drug until the date of death from any cause. For a participant who was not known to have died by the end of study follow-up, OS was censored at the date of last contact. OS was calculated using Kaplan-Meier method and therefore data are estimated.

Event Free Survival (EFS)

EFS was defined as the time from the date of first dose of study drug until the date of documented relapse, treatment failure or death from any cause, whichever occurred first. For a participant with none of these events, EFS was censored at the date of last relapse-free disease assessment. A participant without post-treatment disease assessment was censored at randomization date. Treatment failure included those participants who discontinued the treatment due to "progressive disease" or "lack of efficacy" without a previous response of CR, CRp, CRi or PR. Treatment failure date referred to the start of new anti-leukemia therapy or the last treatment evaluation date when new anti-leukemia therapy date was not available. For participants who were censored, last relapse-free disease assessment date referred to the participant's last disease assessment date. EFS was calculated using Kaplan-Meier method and therefore data are estimated.

Leukemia Free Survival (LFS)

LFS was defined as the time from the date of first CRc until the date of documented relapse or death for participants who achieved CRc. For a participant who was not known to have relapsed or died, LFS was censored on the date of last relapse-free disease assessment date. LFS was calculated using Kaplan-Meier method and therefore data are estimated.

Percentage of Participants Who Achieved Transfusion Conversion

Participants who achieved transfusion conversion were defined as the number of participants who were transfusion dependent at baseline period but became transfusion independent at post-baseline period divided by the total number of participants who were transfusion dependent at baseline period. Participants were considered baseline transfusion dependent if there were RBC or platelet transfusions within the baseline period. Participants were considered post-baseline transfusion independent if they were on treatment >=84 days, and if there was one consecutive 56 days without any RBC or platelet transfusion within post-baseline period. If participants were on treatment >28 days but <84 days, and there was no RBC or platelet transfusion within post-baseline period, or on treatment <=28 days, post-baseline transfusion status was not evaluable. Exact 95% confidence interval was estimated using the binomial distribution.

Percentage of Participants Who Achieved Transfusion Maintenance

Participants who achieved transfusion maintenance were defined as the number of participants who were transfusion independent at baseline period and still maintained transfusion independent at post-baseline period divided by the total number of participants who were transfusion independent at baseline period.

AUC24 of Gilteritinib in Co-administration With Voriconazole

Plasma samples were used for pharmacokinetic assessments.

Cmax of Gilteritinib in Co-administration With Voriconazole

Plasma samples were used for pharmacokinetic assessments.

AUClast of Gilteritinib in Co-administration With Voriconazole

Plasma samples were used for pharmacokinetic assessments.

Tmax of Gilteritinib in Co-administration With Voriconazole

Plasma samples were used for pharmacokinetic assessments.

AUC24 of Midazolam Administered With and Without Gilteritinib

Plasma samples were used for pharmacokinetic assessments.

AUC24 of Metabolite 1-Hydroxymidazolam After Administration of Midazolam With and Without Gilteritinib

Plasma samples were used for pharmacokinetic assessments.

Cmax of Midazolam Administered With and Without Gilteritinib

Plasma samples were used for pharmacokinetic assessments.

Cmax of 1-Hydroxymidazolam After Administration of Midazolam With and Without Gilteritinib

Plasma samples were used for pharmacokinetic assessments.

AUClast of Midazolam Administered With and Without Gilteritinib

Plasma samples were used for pharmacokinetic assessments.

AUClast of 1-Hydroxymidazolam After Administration of Midazolam With and Without Gilteritinib

Plasma samples were used for pharmacokinetic assessments.

Tmax of Midazolam Administered With and Without Gilteritinib

Plasma samples were used for pharmacokinetic assessments.

Tmax of 1-Hydroxymidazolam After Administration of Midazolam With and Without Gilteritinib

Plasma samples were used for pharmacokinetic assessments.

Area Under the Concentration-time Curve From the Time of Dosing Extrapolated to Time Infinity (AUCinf) of Cephalexin Administered With and Without Gilteritinib

Plasma samples were used for pharmacokinetic assessments.

Cmax of Cephalexin Administered With and Without Gilteritinib

Plasma samples were used for pharmacokinetic assessments.

AUClast of Cephalexin Administered With and Without Gilteritinib

Plasma samples were used for pharmacokinetic assessments.

Tmax of Cephalexin Administered With and Without Gilteritinib

Plasma samples were used for pharmacokinetic assessments.

T1/2 of Cephalexin Administered With and Without Gilteritinib

Plasma samples were used for pharmacokinetic assessments.

Apparent Total Systemic Clearance After Single or Multiple Extravascular Dosing (CL/F) of Cephalexin Administered With and Without Gilteritinib

Plasma samples were used for pharmacokinetic assessments.

Apparent Volume of Distribution During the Terminal Elimination Phase After Single Extravascular Dosing (Vz/F) of Cephalexin Administered With and Without Gilteritinib

Plasma samples were used for pharmacokinetic assessments.

Amount of Drug Excreted in Urine (Aelast) of Cephalexin Administered With and Without Gilteritinib

Urine samples were used for pharmacokinetic assessments.

Fraction of Drug Excreted Into Urine in Percentage (%Ae) of Cephalexin Administered With and Without Gilteritinib

Urine samples were used for pharmacokinetic assessments.

Renal Clearance (CLr) of Cephalexin in Administered With and Without Gilteritinib

Urine samples were used for pharmacokinetic assessments.

Full Information

NCT ID

NCT02014558

First Posted

November 6, 2013

Last Updated

May 9, 2019

Sponsor

Astellas Pharma Global Development, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT02014558

Brief Title

Dose Escalation Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics of ASP2215 in Patients With Relapsed or Refractory Acute Myeloid Leukemia

Official Title

A Phase 1/2 Open-Label, Dose Escalation Study Investigating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ASP2215 in Patients With Relapsed or Refractory Acute Myeloid Leukemia

Study Type

Interventional

2. Study Status

Record Verification Date

May 2019

Overall Recruitment Status

Completed

Study Start Date

October 9, 2013 (Actual)

Primary Completion Date

August 4, 2017 (Actual)

Study Completion Date

March 7, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Astellas Pharma Global Development, Inc.

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The objective of this study was to assess the safety and tolerability, including the maximum tolerated dose, of gilteritinib in participants with relapsed or treatment-refractory acute myeloid leukemia (AML). This study also determined the pharmacokinetic (PK) parameters of gilteritinib.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Myeloid Leukemia

Keywords

Acute Myeloid Leukemia, Gilteritinib, ASP2215

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

265 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Gilteritinib 20 mg in Escalation Phase

Arm Type

Experimental

Arm Description

Arm Title

Gilteritinib 40 mg in Escalation Phase

Arm Type

Experimental

Arm Description

Arm Title

Gilteritinib 80 mg in Escalation Phase

Arm Type

Experimental

Arm Description

Arm Title

Gilteritinib 120 mg in Escalation Phase

Arm Type

Experimental

Arm Description

Arm Title

Gilteritinib 200 mg in Escalation Phase

Arm Type

Experimental

Arm Description

Arm Title

Gilteritinib 300 mg in Escalation Phase

Arm Type

Experimental

Arm Description

Arm Title

Gilteritinib 450 mg in Escalation Phase

Arm Type

Experimental

Arm Description

Arm Title

Gilteritinib 20 mg in Expansion Phase

Arm Type

Experimental

Arm Description

Arm Title

Gilteritinib 40 mg in Expansion Phase

Arm Type

Experimental

Arm Description

Arm Title

Gilteritinib 80 mg in Expansion Phase

Arm Type

Experimental

Arm Description

Arm Title

Gilteritinib 120 mg in Expansion Phase

Arm Type

Experimental

Arm Description

Arm Title

Gilteritinib 200 mg in Expansion Phase

Arm Type

Experimental

Arm Description

Arm Title

Gilteritinib 300 mg in Expansion Phase

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Gilteritinib

Other Intervention Name(s)

ASP2215

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Voriconazole

Intervention Description

Participants received 200 mg voriconazole tablets daily every 12 hours starting from day 16 of cycle 1 through day 1 of cycle 2.

Intervention Type

Drug

Intervention Name(s)

Midazolam

Intervention Description

Participants received a single oral dose of 2 mg of midazolam syrup on day -1 and day 15 of cycle 1.

Intervention Type

Drug

Intervention Name(s)

Cephalexin

Intervention Description

Participants received a single oral dose of 500 mg cephalexin tablet or capsule on day -1 and day 15 of cycle 1.

Primary Outcome Measure Information:

Title

Number of Participants With Dose Limiting Toxicities (DLTs)

Description

Time Frame

From first dose up to end of cycle 1 (30 days)

Title

Number of Participants With Adverse Events (AEs)

Description

Time Frame

From first dose of study drug up to 30 days after last dose of study drug (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Title

Area Under the Concentration-time Curve Over the 24-Hour Dosing Interval (AUC24) After Single and Multiple Doses of Gilteritinib

Description

Plasma samples were used for pharmacokinetic assessments.

Time Frame

Day -2 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose

Title

Maximum Concentration (Cmax) After Single and Multiple Doses of Gilteritinib

Description

Plasma samples were used for pharmacokinetic assessments.

Time Frame

Day -2 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose

Title

Area Under the Concentration-time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) After Single and Multiple Doses of Gilteritinib

Description

Plasma samples were used for pharmacokinetic assessments.

Time Frame

Day -2 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose

Title

Time to Observed Cmax (Tmax) After Single and Multiple Doses of Gilteritinib

Description

Plasma samples were used for pharmacokinetic assessments.

Time Frame

Day -2 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose

Title

Terminal Elimination Half-life (t1/2) After Multiple Doses of Gilteritinib

Description

Plasma samples were used for pharmacokinetic assessments.

Time Frame

Cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose

Title

Accumulation Ratio After Multiple Doses of Gilteritinib

Description

Plasma samples were used for pharmacokinetic assessments.

Time Frame

Cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose

Secondary Outcome Measure Information:

Title

Percentage of Participants With Complete Remission (CR) During the First 2 Cycles

Description

Time Frame

During the first 2 cycles (56 days)

Title

Percentage of Participants With CR During Treatment

Description

Time Frame

Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Title

Percentage of Participants With CR With Incomplete Platelet Recovery (CRp)

Description

Time Frame

Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Title

Percentage of Participants With CR With Incomplete Hematological Recovery (CRi)

Description

Time Frame

Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Title

Percentage of Participants With Complete Remission With Partial Hematologic Recovery (CRh)

Description

Time Frame

Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Title

Percentage of Participants With Composite CR (CRc)

Description

Time Frame

Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Title

Percentage of Participants With Partial Remission (PR)

Description

Time Frame

Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Title

Percentage of Participants With Best Response

Description

Time Frame

Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Title

Percentage of Participants With Complete Remission and Complete Remission With Partial Hematologic Recovery (CR/CRh)

Description

Time Frame

Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Title

Duration of CR (DCR)

Description

Time Frame

From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Title

Duration of CRp (DCRp)

Description

Time Frame

From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Title

Duration of CRi (DCRi)

Description

Time Frame

From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Title

Duration of CRh (DCRh)

Description

Time Frame

From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Title

Duration of CRc (DCRc)

Description

Time Frame

From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Title

Duration of CR/CRh (DCRCRh)

Description

Time Frame

From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Title

Duration of Response

Description

Time Frame

From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Title

Time to CR (TTCR)

Description

TTCR was defined as the time from the first dose of study drug until the date of first CR.

Time Frame

From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Title

Time to CRp (TTCRp)

Description

TTCRp was defined as the time from the first dose of study drug until the date of first CRp. TTCRp was evaluated for participants who achieved CRp.

Time Frame

From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Title

Time to CRi (TTCRi)

Description

TTCRi was defined as the time from the first dose of study drug until the date of first CRi. TTCRi was evaluated for participants who achieved CRi.

Time Frame

From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Title

Time to First CR/CRh (TTFCRCRh)

Description

Time Frame

From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Title

Time to Best CR/CRh (TTBCRCRh)

Description

Time Frame

From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Title

Time to CRc (TTCRc)

Description

TTCRc was defined as the time from the first dose of study drug until the date of first CRc. TTCRc was evaluated for participants who achieved CRc.

Time Frame

From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Title

Time to Response (TTR)

Description

TTR was defined as the time from the first dose of study drug until the date of either first CRc or PR. TTR was evaluated for participants who achieved CRc or PR.

Time Frame

From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Title

Time to Best Response (TTBR)

Description

Time Frame

From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Title

Overall Survival (OS)

Description

Time Frame

From first dose of study drug up to end of study (median time on study was 157.0 days, minimum of 5 days and maximum of 1320 days)

Title

Event Free Survival (EFS)

Description

Time Frame

From first dose of study drug up to end of study (median time on study was 157.0 days, minimum of 5 days and maximum of 1320 days)

Title

Leukemia Free Survival (LFS)

Description

Time Frame

From first dose of study drug up to end of study (median time on study was 157.0 days, minimum of 5 days and maximum of 1320 days)

Title

Percentage of Participants Who Achieved Transfusion Conversion

Description

Time Frame

Baseline (28 days prior to first dose until 28 days after the first dose) and postbaseline (from 29 days after first dose date until last dose date); median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days

Title

Percentage of Participants Who Achieved Transfusion Maintenance

Description

Time Frame

Title

AUC24 of Gilteritinib in Co-administration With Voriconazole

Description

Plasma samples were used for pharmacokinetic assessments.

Time Frame

Cycle 1 Day 15 and Cycle 2 Day 1: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (gilteritinib)

Title

Cmax of Gilteritinib in Co-administration With Voriconazole

Description

Plasma samples were used for pharmacokinetic assessments.

Time Frame

Cycle 1 Day 15 and Cycle 2 Day 1: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (gilteritinib)

Title

AUClast of Gilteritinib in Co-administration With Voriconazole

Description

Plasma samples were used for pharmacokinetic assessments.

Time Frame

Cycle 1 Day 15 and Cycle 2 Day 1: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (gilteritinib)

Title

Tmax of Gilteritinib in Co-administration With Voriconazole

Description

Plasma samples were used for pharmacokinetic assessments.

Time Frame

Cycle 1 Day 15 and Cycle 2 Day 1: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (gilteritinib)

Title

AUC24 of Midazolam Administered With and Without Gilteritinib

Description

Plasma samples were used for pharmacokinetic assessments.

Time Frame

Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam)

Title

AUC24 of Metabolite 1-Hydroxymidazolam After Administration of Midazolam With and Without Gilteritinib

Description

Plasma samples were used for pharmacokinetic assessments.

Time Frame

Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam)

Title

Cmax of Midazolam Administered With and Without Gilteritinib

Description

Plasma samples were used for pharmacokinetic assessments.

Time Frame

Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam)

Title

Cmax of 1-Hydroxymidazolam After Administration of Midazolam With and Without Gilteritinib

Description

Plasma samples were used for pharmacokinetic assessments.

Time Frame

Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam)

Title

AUClast of Midazolam Administered With and Without Gilteritinib

Description

Plasma samples were used for pharmacokinetic assessments.

Time Frame

Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam)

Title

AUClast of 1-Hydroxymidazolam After Administration of Midazolam With and Without Gilteritinib

Description

Plasma samples were used for pharmacokinetic assessments.

Time Frame

Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam)

Title

Tmax of Midazolam Administered With and Without Gilteritinib

Description

Plasma samples were used for pharmacokinetic assessments.

Time Frame

Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam)

Title

Tmax of 1-Hydroxymidazolam After Administration of Midazolam With and Without Gilteritinib

Description

Plasma samples were used for pharmacokinetic assessments.

Time Frame

Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam)

Title

Area Under the Concentration-time Curve From the Time of Dosing Extrapolated to Time Infinity (AUCinf) of Cephalexin Administered With and Without Gilteritinib

Description

Plasma samples were used for pharmacokinetic assessments.

Time Frame

Day -1 and cycle 1 day 15: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours postdose (cephalexin)

Title

Cmax of Cephalexin Administered With and Without Gilteritinib

Description

Plasma samples were used for pharmacokinetic assessments.

Time Frame

Day -1 and cycle 1 day 15: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours postdose (cephalexin)

Title

AUClast of Cephalexin Administered With and Without Gilteritinib

Description

Plasma samples were used for pharmacokinetic assessments.

Time Frame

Day -1 and cycle 1 day 15: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours postdose (cephalexin)

Title

Tmax of Cephalexin Administered With and Without Gilteritinib

Description

Plasma samples were used for pharmacokinetic assessments.

Time Frame

Day -1 and cycle 1 day 15: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours postdose (cephalexin)

Title

T1/2 of Cephalexin Administered With and Without Gilteritinib

Description

Plasma samples were used for pharmacokinetic assessments.

Time Frame

Day -1 and cycle 1 day 15: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours postdose (cephalexin)

Title

Apparent Total Systemic Clearance After Single or Multiple Extravascular Dosing (CL/F) of Cephalexin Administered With and Without Gilteritinib

Description

Plasma samples were used for pharmacokinetic assessments.

Time Frame

Day -1 and cycle 1 day 15: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours postdose (cephalexin)

Title

Apparent Volume of Distribution During the Terminal Elimination Phase After Single Extravascular Dosing (Vz/F) of Cephalexin Administered With and Without Gilteritinib

Description

Plasma samples were used for pharmacokinetic assessments.

Time Frame

Day -1 and cycle 1 day 15: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours postdose (cephalexin)

Title

Amount of Drug Excreted in Urine (Aelast) of Cephalexin Administered With and Without Gilteritinib

Description

Urine samples were used for pharmacokinetic assessments.

Time Frame

Day -1 and cycle 1 day 15: 0-3 hours, 3-6 hours, 6-24 hours postdose (cephalexin)

Title

Fraction of Drug Excreted Into Urine in Percentage (%Ae) of Cephalexin Administered With and Without Gilteritinib

Description

Urine samples were used for pharmacokinetic assessments.

Time Frame

Day -1 and cycle 1 day 15: 0-3 hours, 3-6 hours, 6-24 hours postdose (cephalexin)

Title

Renal Clearance (CLr) of Cephalexin in Administered With and Without Gilteritinib

Description

Urine samples were used for pharmacokinetic assessments.

Time Frame

Day -1 and cycle 1 day 15: 0-3 hours, 3-6 hours, 6-24 hours postdose (cephalexin)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Subject is defined as morphologically documented primary or secondary AML by the World Health Organization (WHO) criteria (2008) and fulfills one of the following: 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 was diagnosed as acute promyelocytic leukemia (APL). 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Executive Medical Director

Organizational Affiliation

Astellas Pharma Global Development

Official's Role

Study Director

Facility Information:

Facility Name

Site US10021

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35294

Country

United States

Facility Name

Site US10023

City

Scottsdale

State/Province

Arizona

ZIP/Postal Code

85259

Country

United States

Facility Name

Site US10022

City

Duarte

State/Province

California

ZIP/Postal Code

91010

Country

United States

Facility Name

Site US10008

City

Los Angeles

State/Province

California

ZIP/Postal Code

90095-1678

Country

United States

Facility Name

Site US10005

City

San Francisco

State/Province

California

ZIP/Postal Code

94143

Country

United States

Facility Name

Site US10001

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611

Country

United States

Facility Name

Site US10015

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60637

Country

United States

Facility Name

Site US10012

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21201

Country

United States

Facility Name

Site US10003

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21287

Country

United States

Facility Name

Site US10006

City

Minneapolis

State/Province

Minnesota

ZIP/Postal Code

55455

Country

United States

Facility Name

Site US10011

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

Facility Name

Site US10020

City

Hackensack

State/Province

New Jersey

ZIP/Postal Code

07601

Country

United States

Facility Name

Site US10010

City

Buffalo

State/Province

New York

ZIP/Postal Code

14263

Country

United States

Facility Name

Site US10009

City

New York

State/Province

New York

ZIP/Postal Code

10022

Country

United States

Facility Name

Site US10013

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

Facility Name

Site US10019

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

Facility Name

Site US10014

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44195

Country

United States

Facility Name

Site US10018

City

Hershey

State/Province

Pennsylvania

ZIP/Postal Code

17033

Country

United States

Facility Name

Site US10004

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

Facility Name

Site US10017

City

Charleston

State/Province

South Carolina

ZIP/Postal Code

29425-8900

Country

United States

Facility Name

Site US10007

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37232

Country

United States

Facility Name

Site US10002

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Facility Name

Site US10026

City

Fairfax

State/Province

Virginia

ZIP/Postal Code

22031

Country

United States

Facility Name

Site DE49002

City

Berlin

ZIP/Postal Code

12203

Country

Germany

Facility Name

Site DE49004

City

Dresden

ZIP/Postal Code

01307

Country

Germany

Facility Name

Site IT39001

City

Bologna

ZIP/Postal Code

40138

Country

Italy

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.

IPD Sharing Time Frame

Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.

IPD Sharing Access Criteria

Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.

IPD Sharing URL

https://www.clinicalstudydatarequest.com/

Citations:

PubMed Identifier

32304015

Citation

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. Erratum In: Clin Pharmacokinet. 2021 Sep;60(9):1251.

Results Reference

derived

PubMed Identifier

28645776

Citation

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. Erratum In: Lancet Oncol. 2017 Dec;18(12 ):e711. Lancet Oncol. 2018 Jul;19(7):e335. Lancet Oncol. 2019 Jun;20(6):e293.

Results Reference

derived

PubMed Identifier

26904404

Citation

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.

Results Reference

derived

Links:

URL

https://astellasclinicalstudyresults.com/study.aspx?ID=303

Description

Link to results on the Astellas Clinical Study Results website

Learn more about this trial

Dose Escalation Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics of ASP2215 in Patients With Relapsed or Refractory Acute Myeloid Leukemia

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Dose Escalation Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics of ASP2215 in Patients With Relapsed or Refractory Acute Myeloid Leukemia

Acute Myeloid Leukemia

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial