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A Study of E6201 for the Treatment of Advanced Hematologic Malignancies With FLT3 and/or Ras Mutations

Sponsor
Spirita Oncology, LLC (Industry)
Overall Status
Terminated
CT.gov ID
NCT02418000
Collaborator
(none)
27
Enrollment
4
Locations
5
Arms
26
Duration (Months)
6.8
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase 1/2a dose-escalation study of E6201, a dual mitogen-activated protein kinase/extracellular-signal regulated kinase 1 (MEK1) and FMS-like tyrosine kinase 3 (FLT3) inhibitor, in subjects with advanced hematologic malignancies with documented FLT3 and/or rat sarcoma (Ras) mutations. The Phase1 portion of the study will be a safety run-in (up to 30 subjects) to establish a recommended Phase 2 dose (RP2D). The Ph. 2a portion of the study will evaluate three specific patients groups: Cohort 1 will enroll patients with relapsed or refractory AML and confirmed FLT3 mutation (with or without a Ras mutation) without prior exposure to a FLT3 inhibitor; Cohort 2 will enroll patients with relapsed or refractory AML and confirmed FLT3 mutation (with or without a Ras mutation) with prior exposure to a FLT3 inhibitor; Cohort 3 will enroll patients with relapsed or refractory AML with a confirmed Ras mutation and no FLT3 mutation.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Detailed Description

Phase 1 (Safety Run-In): Following Screening, a total of up to 30 subjects in up to 5 dose cohorts to establish the RP2D. The safety run-in phase will be a standard 3+3 cohort design.

Phase 2a (Expansion): Once the Phase 1 Safety Run-In portion of the study is complete and an RP2D is established, additional subjects will be enrolled into the Phase 2 Expansion portion in three cohorts. Cohort 1 will enroll up to 26 patients with relapsed or refractory AML and confirmed FLT3 mutation (with or without a Ras mutation) without prior exposure to a FLT3 inhibitor. Cohort 2 will enroll up to 26 patients with relapsed or refractory AML and confirmed FLT3 mutation (with or without a Ras mutation) with prior exposure to a FLT3 inhibitor. Cohort 3 will enroll up to 10 patients with relapsed or refractory AML with a confirmed Ras mutation and no FLT3 mutation. Cohort 1 and 2 of the Expansion Phase will incorporate a Simon 2-stage optimal design. Subjects with AML enrolled in the Phase 1 portion of the study at the RP2D will count towards the Phase 2a accrual for the appropriate cohort.

Subjects will receive E6201 weekly or bi-weekly on a 28-day schedule, with the schedule and dose level established in the Safety Run-In portion of the study. Disease assessments, including analysis of blood and bone marrow samples, will be performed at the end of Cycles 1 and 3 and every 2 cycles thereafter. Disease assessments may be made at other time points at the discretion of the Investigator.

Subjects who demonstrate clinical benefit (objective response or stable disease) will be allowed to continue therapy with E6201 until progression of disease, observation of unacceptable adverse events, intercurrent illness or changes in the patient's condition that prevents further study participation.

During the study, ECGs will be performed, blood will be collected for hematology, serum chemistry, pharmacokinetics and pharmacodynamics assessments, and bone marrow will be collected for the assessment of disease response and mutational status.

Study Design

Study Type:
Interventional
Actual Enrollment :
27 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/2a Study of E6201 for the Treatment of Advanced Hematologic Malignancies With FLT3 and/or Ras Mutations, Including Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML)
Study Start Date :
Apr 10, 2015
Actual Primary Completion Date :
Jun 8, 2017
Actual Study Completion Date :
Jun 8, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: E6201 240 mg/m^2 IV weekly

E6201 240 mg/m^2 administered IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle)

Drug: E6201
Single Group Assignment
Other Names:
  • Dual inhibitor of FLT3 and MEK1

    		•
    Experimental: E6201 320 mg/m^2 IV weekly

    E6201 320 mg/m^2 administered IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle)

    Drug: E6201
    Single Group Assignment
    Other Names:
  • Dual inhibitor of FLT3 and MEK1

    		•
    Experimental: E6201 160 mg/m^2 IV twice weekly

    E6201 160 mg/m^2 administered IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle)

    Drug: E6201
    Single Group Assignment
    Other Names:
  • Dual inhibitor of FLT3 and MEK1

    		•
    Experimental: E6201 240 mg/m^2 IV twice weekly

    E6201 240 mg/m^2 administered IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle)

    Drug: E6201
    Single Group Assignment
    Other Names:
  • Dual inhibitor of FLT3 and MEK1

    		•
    Experimental: E6201 320 mg/m^2 IV twice weekly

    E6201 320 mg/m^2 administered IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22, and 25, repeated every 28 days (= 1 cycle)

    Drug: E6201
    Single Group Assignment
    Other Names:
  • Dual inhibitor of FLT3 and MEK1

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Maximum Tolerated Dose (MTD) of E6201 [Up to 6 weeks for each dose cohort]

      Phase 1 (Safety Run-In) was conducted in 5 dose cohorts in up to 30 subjects in a standard 3+3 dose-escalation design to establish an MTD and recommended Phase 2 dose (RP2D). Safety assessed through the monitoring of adverse events (AEs), serious adverse events (SAEs), clinical laboratory parameters (hematology and serum chemistry), vital sign measurements, electrocardiograms (ECGs) and physical examinations.

    2. Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) [Up to 6 weeks for each dose cohort]

      A DLT was defined as any one of the following events: prolonged myelosuppression (as defined by the National Cancer Institute [NCI] criteria specific for leukemia, i.e., marrow cellularity < 5% at ≥ 6 weeks from start of therapy without evidence of leukemia); ≥ Grade 3 non-hematologic toxicity (excluding Grade 3 nausea, vomiting or diarrhea that is adequately controlled with supportive care and resolves to ≤ Grade 2 within 48 hours, or Grade 3 electrolyte disturbances responsive to correction within 24 hours); ≥ Grade 3 liver function tests (LFTs) lasting > 7 days; treatment interruption > 14 days due to toxicity; or other important medical event. DLTs were collected to determine the MTD which is defined as the dose level below the dose at which ≥ 2 of 6 patients in a dose cohort experienced a DLT.

    Secondary Outcome Measures

    1. Overall Response Rate [At the end of C1 and every 2 cycles thereafter through 6 months following last dose of study drug]

      For acute myeloid leukemia (AML): Revised Recommendations of the International Working Group (IWG) Response Criteria for AML: CR: Free of leukemia-related symptoms, absolute neutrophil count (ANC) > 1.0 x 10^9/L, platelet count ≥ 100 x 10^9/L, normal bone marrow with < 5% blasts and no Auer rods. CRi: As per CR but w/ residual thrombocytopenia (platelet count <100 x 10^9/L) or residual neutropenia (ANC <1.0 x 10^9/L). PR: ≥50% decrease bone marrow blasts to 5 - 25% abnormal cells, or CR w/ ≤ 5% blasts if Auer rods present. For myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML): Modified IWG Response Criteria for MDS: CR: Free of leukemia-related symptoms, ANC ≥1.0 x 10^9/L, platelet count ≥100 x 10^9/L, bone marrow ≤5% myeloblasts, normal maturation of all cell lines, hemoglobin ≥ 11g/dL, no blasts in the peripheral blood. PR: All CR criteria w/ ≥50% decrease in bone marrow blasts over pre-treatment, but still > 5%.

    2. Duration of Response [At the end of C1 and every 2 cycles thereafter through 6 months following last dose of study drug]

      Length of time from the first evidence of objective response to the first evidence of progression

    3. Progression-Free Survival [From Cycle 1 Day 1 (C1D1) until death or study closure, up to 26 months]

      Length of time from the date of first administration of study drug to the first evidence of disease progression or death, whichever is earlier

    4. Overall Survival [From C1D1 until death or study closure, up to 26 months]

      Length of time from the date of first administration of study drug to the date of death from any cause

    5. Pharmacokinetic Profile of E6201 in Plasma: Cmax [Assessed at Cycle 1 Days 1 and 15, Cycle 2 Day 1, pre-dose, 5 minutes following the end of the 2-hour infusion, 2, 4, 8 and 24 hours post-infusion. Summary PK parameters for Cycle 1 Day 1 reported.]

      Cmax: Maximum measured plasma concentration over the collection period

    6. Pharmacokinetics of E6201 in Plasma: Tmax [Assessed at Cycle 1 Days 1 and 15, Cycle 2 Day 1, pre-dose, 5 minutes following the end of the 2-hour infusion, 2, 4, 8 and 24 hours post-infusion. Summary PK parameters for Cycle 1 Day 1 reported.]

      Tmax: Time to maximum measured plasma concentration

    7. Pharmacokinetic Profile of E6201 in Plasma: AUCT [Assessed at Cycle 1 Days 1 and 15, Cycle 2 Day 1, pre-dose, 5 minutes following the end of the 2-hour infusion, 2, 4, 8 and 24 hours post-infusion. Summary PK parameters for Cycle 1 Day 1 reported.]

      Area under the plasma concentration versus time curve (AUC) to the last measurable concentration over the sampling time-interval.

    8. Pharmacokinetic Profile of E6201 in Plasma: AUCI [Assessed at Cycle 1 Days 1 and 15, Cycle 2 Day 1, pre-dose, 5 minutes following the end of the 2-hour infusion, 2, 4, 8 and 24 hours post-infusion. Summary PK parameters for Cycle 1 Day 1 reported.]

      AUCI: The area under the concentration versus time curve from time 0 to infinity

    9. Pharmacokinetic Profile of E6201 in Plasma: T1/2 [Assessed at Cycle 1 Days 1 and 15, Cycle 2 Day 1, pre-dose, 5 minutes following the end of the 2-hour infusion, 2, 4, 8 and 24 hours post-infusion. Summary PK parameters for Cycle 1 Day 1 reported.]

      T1/2: The apparent first-order elimination half-life

    10. Pharmacokinetic Profile of E6201 in Plasma: CLobs [Assessed at Cycle 1 Days 1 and 15, Cycle 2 Day 1, pre-dose, 5 minutes following the end of the 2-hour infusion, 2, 4, 8 and 24 hours post-infusion. Summary PK parameters for Cycle 1 Day 1 reported.]

      Clearance observed (CLobs): Total body clearance for extravascular administration

    11. Pharmacokinetic Profile of E6201 in Plasma: VDobs [Assessed at Cycle 1 Days 1 and 15, Cycle 2 Day 1, pre-dose, 5 minutes following the end of the 2-hour infusion, 2, 4, 8 and 24 hours post-infusion. Summary PK parameters for Cycle 1 Day 1 reported.]

      Measurement of apparent volume of distribution observed (VDobs)

    12. Number of Participants With Suppression of pERK at 4 Hours Post-dose [Cycle 1 Day 1, 4 hours post-dose.]

      phospho-ERK (pERK) in blood assessed by Western blot at 4 hours post-dose

    13. Number of Participants With Suppression of pERK at 24 Hours Post-dose [Cycle 1 Day 1, 24 hours post-dose.]

      Measurement of phospho-ERK (pERK) in blood assessed by Western blot at 24 hours post-dose

    14. Number of Participants With Suppression of pFLT3 at 4 Hours Post-dose [Cycle 1 Day 1, 4 hours post-dose.]

      phospho-FLT3 (pFLT3) in blood assessed by Western blot at 4 hours post-dose

    15. Number of Participants With Suppression of pFLT3 at 24 Hours Post-dose [Cycle 1 Day 1, 24 hours post-dose.]

      phospho-FLT3 (pFLT3) in blood assessed by Western blot at 24 hours post-dose

    16. Number of Participants With Suppression of pAKT at 4 Hours Post-dose [Cycle 1 Day 1, 4 hours post-dose.]

      phospho-AKT (pAKT) in blood assessed by Western blot at 4 hours post-dose

    17. Number of Participants With Suppression of pAKT at 24 Hours Post-dose [Cycle 1 Day 1, 24 hours post-dose.]

      phospho-AKT (pAKT) in blood assessed by Western blot at 24 hours post-dose

    18. Number of Participants With Suppression of pERK by PIA at 4 Hours Post-dose [Cycle 1 Day 1, 4 hours post-dose.]

      Blood assay: Plasma inhibitory assay (PIA) measuring pERK in blood at 4 hours post-dose

    19. Number of Participants With Suppression of in pERK by PIA 24 Hours Post-dose [Cycle 1 Day 1, 24 hours post-dose.]

      Blood assay: Plasma inhibitory assay (PIA) measuring pERK in blood at 24 hours post-dose

    20. Number of Participants With Suppression of pFLT3 by PIA at 4 Hours Post-dose [Cycle 1 Day 1, 4 hours post-dose.]

      Blood assay: Plasma inhibitory assay (PIA) measuring pFLT3 in blood at 4 hours post-dose

    21. Number of Participants With Suppression of pFLT3 by PIA at 24 Hours Post-dose [Cycle 1 Day 1, 24 hours post-dose.]

      Blood assay: Plasma inhibitory assay (PIA) measuring pFLT3 in blood at 24 hours post-dose

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Males and females ≥ 18 years of age

    • Phase 1: Confirmed relapsed or refractory AML with a documented FLT3 and/or Ras mutation, or ≥ 60 years with newly diagnosed FLT3+ and/or Ras+ AML and not eligible for standard induction chemotherapy or FLT3+ and/or Ras+ higher-risk MDS/CMML (defined as ≥ 10% marrow blasts or ≥ 5% peripheral blood blasts or Revised International Prognostic Scoring System [IPSS-R] score ≥ 3.5) and relapsed or refractory to prior therapy

    • Phase 2: Confirmed relapsed or refractory AML with a documented FLT3 and/or Ras mutation, or age ≥ 60 years with newly diagnosed FLT3+ and/or Ras+ AML and not eligible for standard induction chemotherapy

    • At least 3 weeks beyond the last cancer treatment for the disease under study, major surgery and recovered from all acute toxicities (≤ Grade 1) by first dose of study drug (C1D1). Hydroxyurea used to control peripheral blast counts is permitted during the first 2 cycles.

    • Adequate performance status Eastern Cooperative Oncology Group (ECOG) ≤ 2

    • Adequate renal and hepatic function:

    • creatinine ≤ 1.5 mg/dL OR calculated creatinine clearance ≥ 45 mL/minute

    • total bilirubin ≤ 2 times the upper limit of normal (ULN) unless due to Gilbert's disease or thought to be due to underlying AML

    • ALT and AST ≤ 5 times ULN

    • Negative serum pregnancy test within 14 days prior to the first dose of study therapy for women of child-bearing potential (WCBP). Sexually active WCBP and male subjects must agree to use adequate methods to avoid pregnancy throughout the study and for 28 days after completion of study treatment.

    • Ability to provide written informed consent

    Exclusion Criteria:

    • History of clinically significant cardiac impairment, congestive heart failure (CHF) New York Heart Association (NYHA) Class III or IV, unstable angina, or myocardial infarction during the previous 6 months, or serious cardiac arrhythmia

    • QT interval corrected for rate (QTc) ≥ 450 msec for males and ≥ 460 msec for females on the ECG obtained at Screening using Fridericia method for QTc calculation (average of 3 readings)

    • Concomitant medication(s) that may cause QTc prolongation or induce Torsades de Pointes with the exception of anti-microbials used as standard of care to prevent or treat infections and other such drugs that are considered by the investigator to be essential for the care of the patient. However, if such medications are deemed to be necessary during the study, more extensive ECG monitoring will be added during the period of concomitant drug administration.

    • Presence of active central nervous system (CNS) leukemia. Subjects adequately treated for CNS leukemia documented by 2 consecutive cerebrospinal fluid samples negative for leukemia cells are eligible. Subjects with no history of CNS leukemia will not be required to undergo cerebrospinal fluid sampling for eligibility.

    • Known positive for human immunodeficiency virus (HIV), hepatitis B virus surface antigen (HBsAg), or hepatitis C virus HCV)

    • Active, uncontrolled infection

    • Known hypersensitivity to any study drug component

    • History of another malignancy; Exception: Patients disease-free for 2 years or treated in situ carcinoma

    • Any other medical intervention or other condition which, in the opinion of the Principal Investigator, could compromise adherence to study requirements or confound the interpretation of study results

    • Pregnancy or lactation

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Colorado Blood Cancer Institute Denver Colorado United States 80218
    2 H. Lee Moffitt Cancer Center & research Institute Tampa Florida United States 33612
    3 MD Anderson Cancer Center Houston Texas United States 77030
    4 Texas Transplant Institute San Antonio Texas United States 78229

    Sponsors and Collaborators

    • Spirita Oncology, LLC

    Investigators

    • Study Chair: Gautam Borthakur, MD, MD Anderson Cancer Center Houston, TX 77030

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Spirita Oncology, LLC
    ClinicalTrials.gov Identifier:
    NCT02418000
    Other Study ID Numbers:
    • BSC-101-01
    First Posted:
    Apr 16, 2015
    Last Update Posted:
    Mar 20, 2019
    Last Verified:
    Mar 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Hematologic Neoplasms

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title E6201 240 mg/m^2 Weekly E6201 320 mg/m^2 Weekly E6201 160 mg/m^2 Twice Weekly E6201 240 mg/m^2 Twice Weekly E6201 320 mg/m^2 Twice Weekly
    Arm/Group Description Cohort 1: Participants were administered E6201 240 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 2: Participants were administered E6201 320 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 3: Participants were administered E6201 160 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 4: Participants were administered E6201 240 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 5: Participants were administered E6201 320 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose.
    Period Title: Cohort 1: E6201 240 mg/m^2 Weekly
    STARTED 7 0 0 0 0
    COMPLETED 0 0 0 0 0
    NOT COMPLETED 7 0 0 0 0
    Period Title: Cohort 1: E6201 240 mg/m^2 Weekly
    STARTED 0 10 0 0 0
    COMPLETED 0 0 0 0 0
    NOT COMPLETED 0 10 0 0 0
    Period Title: Cohort 1: E6201 240 mg/m^2 Weekly
    STARTED 0 0 3 0 0
    COMPLETED 0 0 0 0 0
    NOT COMPLETED 0 0 3 0 0
    Period Title: Cohort 1: E6201 240 mg/m^2 Weekly
    STARTED 0 0 0 3 0
    COMPLETED 0 0 0 0 0
    NOT COMPLETED 0 0 0 3 0
    Period Title: Cohort 1: E6201 240 mg/m^2 Weekly
    STARTED 0 0 0 0 4
    COMPLETED 0 0 0 0 0
    NOT COMPLETED 0 0 0 0 4

    Baseline Characteristics

    Arm/Group Title Cohort 1: E6201 240 mg/m^2 Weekly Cohort 2: E6201 320 mg/m^2 Weekly Cohort 3: E6201 160 mg/m^2 Twice Weekly Cohort 4: E6201 240 mg/m^2 Twice Weekly Cohort 5: E6201 320 mg/m^2 Twice Weekly Total
    Arm/Group Description Cohort 1: Participants were administered E6201 240 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for study drug discontinued, and followed for up to 6 months after the last dose. Cohort 2: Participants were administered E6201 320 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for study drug discontinuation, and followed for up to 6 months after the last dose. Cohort 3: Participants were administered E6201 160 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for study drug discontinuation, and followed for up to 6 months after the last dose. Cohort 4: Participants were administered E6201 240 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for study drug discontinuation, and followed for up to 6 months after the last dose. Cohort 5: Participants were administered E6201 320 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for study drug discontinuation, and followed for up to 6 months after the last dose. Total of all reporting groups
    Overall Participants 7 10 3 3 4 27
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    61.57
    (13.97)
    51.10
    (19.14)
    61.33
    (11.02)
    56.33
    (12.01)
    56.00
    (17.64)
    56.26
    (15.78)
    Sex: Female, Male (Count of Participants)
    Female
    5
    71.4%
    4
    40%
    2
    66.7%
    1
    33.3%
    2
    50%
    14
    51.9%
    Male
    2
    28.6%
    6
    60%
    1
    33.3%
    2
    66.7%
    2
    50%
    13
    48.1%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    1
    14.3%
    1
    10%
    1
    33.3%
    0
    0%
    0
    0%
    3
    11.1%
    Not Hispanic or Latino
    4
    57.1%
    8
    80%
    2
    66.7%
    3
    100%
    4
    100%
    21
    77.8%
    Unknown or Not Reported
    2
    28.6%
    1
    10%
    0
    0%
    0
    0%
    0
    0%
    3
    11.1%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    1
    33.3%
    1
    25%
    2
    7.4%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    1
    14.3%
    3
    30%
    0
    0%
    0
    0%
    0
    0%
    4
    14.8%
    White
    5
    71.4%
    6
    60%
    3
    100%
    2
    66.7%
    3
    75%
    19
    70.4%
    More than one race
    1
    14.3%
    1
    10%
    0
    0%
    0
    0%
    0
    0%
    2
    7.4%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    7
    100%
    10
    100%
    3
    100%
    3
    100%
    4
    100%
    27
    100%
    Disease Type (Count of Participants)
    AML
    4
    57.1%
    10
    100%
    3
    100%
    3
    100%
    4
    100%
    24
    88.9%
    MDS
    1
    14.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    3.7%
    CMML
    2
    28.6%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    7.4%
    Eastern Cooperative Group (ECOG) Performance Status (Count of Participants)
    0
    2
    28.6%
    1
    10%
    0
    0%
    0
    0%
    0
    0%
    3
    11.1%
    1
    5
    71.4%
    6
    60%
    2
    66.7%
    3
    100%
    4
    100%
    20
    74.1%
    2
    0
    0%
    3
    30%
    1
    33.3%
    0
    0%
    0
    0%
    4
    14.8%
    3
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    4
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Prior Cancer Therapies (Number of treatment regimens) [Median (Full Range) ]
    All Prior Cancer Treatment Regimens
    3
    6.5
    4
    5
    4
    5
    Prior FLT3 Inhibitor Treatment Regimens
    1
    1
    1
    1
    1
    1

    Outcome Measures

    1. Primary Outcome
    Title Maximum Tolerated Dose (MTD) of E6201
    Description Phase 1 (Safety Run-In) was conducted in 5 dose cohorts in up to 30 subjects in a standard 3+3 dose-escalation design to establish an MTD and recommended Phase 2 dose (RP2D). Safety assessed through the monitoring of adverse events (AEs), serious adverse events (SAEs), clinical laboratory parameters (hematology and serum chemistry), vital sign measurements, electrocardiograms (ECGs) and physical examinations.
    Time Frame Up to 6 weeks for each dose cohort

    Outcome Measure Data

    Analysis Population Description
    Full analysis set (FAS): All subjects who were administered any fraction of a dose of study medication
    Arm/Group Title All Participants
    Arm/Group Description All study participants who received at least 1 dose of E6201 at 240 or 320 mg/m^2 IV weekly, or at 160, 240 or 320 mg/m^2 IV twice weekly
    Measure Participants 27
    Number [E6201 MTD (mg/m^2) IV twice weekly]
    320
    2. Primary Outcome
    Title Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
    Description A DLT was defined as any one of the following events: prolonged myelosuppression (as defined by the National Cancer Institute [NCI] criteria specific for leukemia, i.e., marrow cellularity < 5% at ≥ 6 weeks from start of therapy without evidence of leukemia); ≥ Grade 3 non-hematologic toxicity (excluding Grade 3 nausea, vomiting or diarrhea that is adequately controlled with supportive care and resolves to ≤ Grade 2 within 48 hours, or Grade 3 electrolyte disturbances responsive to correction within 24 hours); ≥ Grade 3 liver function tests (LFTs) lasting > 7 days; treatment interruption > 14 days due to toxicity; or other important medical event. DLTs were collected to determine the MTD which is defined as the dose level below the dose at which ≥ 2 of 6 patients in a dose cohort experienced a DLT.
    Time Frame Up to 6 weeks for each dose cohort

    Outcome Measure Data

    Analysis Population Description
    Full analysis set (FAS): All subjects who were administered any fraction of a dose of study medication.
    Arm/Group Title E6201 240 mg/m^2 Weekly E6201 320 mg/m^2 Weekly E6201 160 mg/m^2 Twice Weekly E6201 240 mg/m^2 Twice Weekly E6201 320 mg/m^2 IV Twice Weekly
    Arm/Group Description E6201 240 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. E6201 320 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. E6201 160 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. E6201 240 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. E6201 320 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose.
    Measure Participants 7 10 3 3 4
    Number [Number of Participants with DLTs]
    1
    14.3%
    1
    10%
    0
    0%
    0
    0%
    0
    0%
    3. Secondary Outcome
    Title Overall Response Rate
    Description For acute myeloid leukemia (AML): Revised Recommendations of the International Working Group (IWG) Response Criteria for AML: CR: Free of leukemia-related symptoms, absolute neutrophil count (ANC) > 1.0 x 10^9/L, platelet count ≥ 100 x 10^9/L, normal bone marrow with < 5% blasts and no Auer rods. CRi: As per CR but w/ residual thrombocytopenia (platelet count <100 x 10^9/L) or residual neutropenia (ANC <1.0 x 10^9/L). PR: ≥50% decrease bone marrow blasts to 5 - 25% abnormal cells, or CR w/ ≤ 5% blasts if Auer rods present. For myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML): Modified IWG Response Criteria for MDS: CR: Free of leukemia-related symptoms, ANC ≥1.0 x 10^9/L, platelet count ≥100 x 10^9/L, bone marrow ≤5% myeloblasts, normal maturation of all cell lines, hemoglobin ≥ 11g/dL, no blasts in the peripheral blood. PR: All CR criteria w/ ≥50% decrease in bone marrow blasts over pre-treatment, but still > 5%.
    Time Frame At the end of C1 and every 2 cycles thereafter through 6 months following last dose of study drug

    Outcome Measure Data

    Analysis Population Description
    The analysis population was the per-protocol set (PPS). The PPS included all subjects in the FAS who had a valid baseline and one or more post-treatment assessments for a specified measure.
    Arm/Group Title E6201 240 mg/m^2 Weekly E6201 320 mg/m^2 Weekly E6201 160 mg/m^2 Twice Weekly E6201 240 mg/m^2 Twice Weekly E6201 320 mg/m^2 Twice Weekly
    Arm/Group Description E6201 240 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. E6201 320 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. E6201 160 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. E6201 240 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. E6201 320 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose.
    Measure Participants 7 10 3 3 4
    Number [Objective Responses]
    0
    0
    0
    0
    0
    4. Secondary Outcome
    Title Duration of Response
    Description Length of time from the first evidence of objective response to the first evidence of progression
    Time Frame At the end of C1 and every 2 cycles thereafter through 6 months following last dose of study drug

    Outcome Measure Data

    Analysis Population Description
    The analysis population was the per-protocol set (PPS). The PPS included all subjects in the FAS who had a valid baseline and one or more post-treatment assessments for a specified measure. No objective responses were observed. Therefore, duration of response could not be calculated.
    Arm/Group Title E6201 240 mg/m^2 Weekly E6201 320 mg/m^2 Weekly E6201 160 mg/m^2 Twice Weekly E6201 240 mg/m^2 Twice Weekly E6201 320 mg/m^2 Twice Weekly
    Arm/Group Description E6201 240 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. E6201 320 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. E6201 160 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. E6201 240 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. E6201 320 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose.
    Measure Participants 0 0 0 0 0
    5. Secondary Outcome
    Title Progression-Free Survival
    Description Length of time from the date of first administration of study drug to the first evidence of disease progression or death, whichever is earlier
    Time Frame From Cycle 1 Day 1 (C1D1) until death or study closure, up to 26 months

    Outcome Measure Data

    Analysis Population Description
    The analysis population was the per-protocol set (PPS). The PPS included all subjects in the FAS who had a valid baseline and one or more post-treatment assessments for a specified measure. For AML, MDS and CMML, progression was defined by relevant IWG criteria as failure to achieve at least a PR. No responses; PFS could not be calculated.
    Arm/Group Title E6201 240 mg/m^2 Weekly E6201 320 mg/m^2 Weekly E6201 160 mg/m^2 Twice Weekly E6201 240 mg/m^2 Twice Weekly E6201 320 mg/m^2 Twice Weekly
    Arm/Group Description E6201 240 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. E6201 320 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. E6201 160 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. E6201 240 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. E6201 320 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose.
    Measure Participants 0 0 0 0 0
    6. Secondary Outcome
    Title Overall Survival
    Description Length of time from the date of first administration of study drug to the date of death from any cause
    Time Frame From C1D1 until death or study closure, up to 26 months

    Outcome Measure Data

    Analysis Population Description
    The analysis population was the per-protocol set (PPS). The PPS included all subjects in the FAS who had a valid baseline and one or more post-treatment assessments for a specified endpoint.
    Arm/Group Title E6201 240 mg/m^2 Weekly E6201 320 mg/m^2 Weekly E6201 160 mg/m^2 Twice Weekly E6201 240 mg/m^2 Twice Weekly E6201 320 mg/m^2 Twice Weekly
    Arm/Group Description E6201 240 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. E6201 320 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. E6201 160 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. E6201 240 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. E6201 320 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose.
    Measure Participants 3 9 2 2 3
    Median (Standard Deviation) [Days]
    31
    (13.01)
    68
    (50.39)
    96
    (69.30)
    99
    (48.08)
    30
    (35.37)
    7. Secondary Outcome
    Title Pharmacokinetic Profile of E6201 in Plasma: Cmax
    Description Cmax: Maximum measured plasma concentration over the collection period
    Time Frame Assessed at Cycle 1 Days 1 and 15, Cycle 2 Day 1, pre-dose, 5 minutes following the end of the 2-hour infusion, 2, 4, 8 and 24 hours post-infusion. Summary PK parameters for Cycle 1 Day 1 reported.

    Outcome Measure Data

    Analysis Population Description
    All subjects in the FAS who completed at least 1 pharmacokinetic (PK) assessment.
    Arm/Group Title E6201 240 mg/m^2 Weekly E6201 320 mg/m^2 Weekly E6201 160 mg/m^2 Twice Weekly E6201 240 mg/m^2 Twice Weekly E6201 320 mg/m^2 Twice Weekly
    Arm/Group Description E6201 240 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. E6201 320 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. E6201 160 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. E6201 240 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. E6201 320 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose.
    Measure Participants 7 10 3 3 4
    Mean (Standard Deviation) [ng/mL]
    1195.04
    (10.6)
    1430.39
    (76.2)
    736.87
    (50.7)
    941.66
    (47.7)
    1681.12
    (5.6)
    8. Secondary Outcome
    Title Pharmacokinetics of E6201 in Plasma: Tmax
    Description Tmax: Time to maximum measured plasma concentration
    Time Frame Assessed at Cycle 1 Days 1 and 15, Cycle 2 Day 1, pre-dose, 5 minutes following the end of the 2-hour infusion, 2, 4, 8 and 24 hours post-infusion. Summary PK parameters for Cycle 1 Day 1 reported.

    Outcome Measure Data

    Analysis Population Description
    All subjects in the FAS who completed at least 1 pharmacokinetic (PK) assessment.
    Arm/Group Title E6201 240 mg/m^2 Weekly E6201 320 mg/m^2 Weekly E6201 160 mg/m^2 Twice Weekly E6201 240 mg/m^2 Twice Weekly E6201 320 mg/m^2 Twice Weekly
    Arm/Group Description E6201 240 mg/m^2 administered IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. E6201 320 mg/m^2 administered IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. E6201 160 mg/m^2 administered IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. E6201 240 mg/m^2 administered IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. E6201 320 mg/m^2 administered IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22, and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose.
    Measure Participants 7 10 3 3 4
    Mean (Standard Deviation) [h]
    2.34
    (7.5)
    4.10
    (95.4)
    2.17
    (0.9)
    2.32
    (6.8)
    2.18
    (4.2)
    9. Secondary Outcome
    Title Pharmacokinetic Profile of E6201 in Plasma: AUCT
    Description Area under the plasma concentration versus time curve (AUC) to the last measurable concentration over the sampling time-interval.
    Time Frame Assessed at Cycle 1 Days 1 and 15, Cycle 2 Day 1, pre-dose, 5 minutes following the end of the 2-hour infusion, 2, 4, 8 and 24 hours post-infusion. Summary PK parameters for Cycle 1 Day 1 reported.

    Outcome Measure Data

    Analysis Population Description
    All subjects in the FAS who completed at least 1 pharmacokinetic (PK) assessment.
    Arm/Group Title E6201 240 mg/m^2 Weekly E6201 320 mg/m^2 Weekly E6201 160 mg/m^2 Twice Weekly E6201 240 mg/m^2 Twice Weekly E6201 320 mg/m^2 Twice Weekly
    Arm/Group Description Cohort 1: Participants were administered E6201 240 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 2: Participants were administered E6201 320 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 3: Participants were administered E6201 160 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 4: Participants were administered E6201 240 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 5: Participants were administered E6201 320 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose.
    Measure Participants 7 10 3 3 4
    Mean (Standard Deviation) [h.ng/mL]
    3797.76
    (20.6)
    8135.24
    (88.0)
    3034.10
    (69.8)
    2796.73
    (50.3)
    6082.79
    (23.0)
    10. Secondary Outcome
    Title Pharmacokinetic Profile of E6201 in Plasma: AUCI
    Description AUCI: The area under the concentration versus time curve from time 0 to infinity
    Time Frame Assessed at Cycle 1 Days 1 and 15, Cycle 2 Day 1, pre-dose, 5 minutes following the end of the 2-hour infusion, 2, 4, 8 and 24 hours post-infusion. Summary PK parameters for Cycle 1 Day 1 reported.

    Outcome Measure Data

    Analysis Population Description
    All subjects in the FAS who completed at least 1 pharmacokinetic (PK) assessment.
    Arm/Group Title E6201 240 mg/m^2 Weekly E6201 320 mg/m^2 Weekly E6201 160 mg/m^2 Twice Weekly E6201 240 mg/m^2 Twice Weekly E6201 320 mg/m^2 Twice Weekly
    Arm/Group Description Cohort 1: Participants were administered E6201 240 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 2: Participants were administered E6201 320 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 3: Participants were administered E6201 160 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 4: Participants were administered E6201 240 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 5: Participants were administered E6201 320 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose.
    Measure Participants 7 10 3 3 4
    Mean (Standard Deviation) [h.ng/mL]
    3871.83
    (21.7)
    2506.90
    (56.0)
    1853.13
    (1.1)
    2215.63
    (59.0)
    6388.31
    (25.0)
    11. Secondary Outcome
    Title Pharmacokinetic Profile of E6201 in Plasma: T1/2
    Description T1/2: The apparent first-order elimination half-life
    Time Frame Assessed at Cycle 1 Days 1 and 15, Cycle 2 Day 1, pre-dose, 5 minutes following the end of the 2-hour infusion, 2, 4, 8 and 24 hours post-infusion. Summary PK parameters for Cycle 1 Day 1 reported.

    Outcome Measure Data

    Analysis Population Description
    All subjects in the FAS who completed at least 1 pharmacokinetic (PK) assessment.
    Arm/Group Title E6201 240 mg/m^2 Weekly E6201 320 mg/m^2 Weekly E6201 160 mg/m^2 Twice Weekly E6201 240 mg/m^2 Twice Weekly E6201 320 mg/m^2 Twice Weekly
    Arm/Group Description Cohort 1: Participants were administered E6201 240 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 2: Participants were administered E6201 320 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 3: Participants were administered E6201 160 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 4: Participants were administered E6201 240 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 5: Participants were administered E6201 320 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose.
    Measure Participants 7 10 3 3 4
    Mean (Standard Deviation) [h]
    3.78
    (88.0)
    2.71
    (87.5)
    3.20
    (43.6)
    1.66
    (4.5)
    5.01
    (71.1)
    12. Secondary Outcome
    Title Pharmacokinetic Profile of E6201 in Plasma: CLobs
    Description Clearance observed (CLobs): Total body clearance for extravascular administration
    Time Frame Assessed at Cycle 1 Days 1 and 15, Cycle 2 Day 1, pre-dose, 5 minutes following the end of the 2-hour infusion, 2, 4, 8 and 24 hours post-infusion. Summary PK parameters for Cycle 1 Day 1 reported.

    Outcome Measure Data

    Analysis Population Description
    All subjects in the FAS who completed at least 1 pharmacokinetic (PK) assessment.
    Arm/Group Title E6201 240 mg/m^2 Weekly E6201 320 mg/m^2 Weekly E6201 160 mg/m^2 Twice Weekly E6201 240 mg/m^2 Twice Weekly E6201 320 mg/m^2 Twice Weekly
    Arm/Group Description Cohort 1: Participants were administered E6201 240 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 2: Participants were administered E6201 320 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 3: Participants were administered E6201 160 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 4: Participants were administered E6201 240 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 5: Participants were administered E6201 320 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose.
    Measure Participants 7 10 3 3 4
    Mean (Standard Deviation) [L/h]
    104.0
    (17.8)
    300.2
    (45.3)
    150.68
    (15.3)
    221.2
    (70.1)
    85.7
    (33.1)
    13. Secondary Outcome
    Title Pharmacokinetic Profile of E6201 in Plasma: VDobs
    Description Measurement of apparent volume of distribution observed (VDobs)
    Time Frame Assessed at Cycle 1 Days 1 and 15, Cycle 2 Day 1, pre-dose, 5 minutes following the end of the 2-hour infusion, 2, 4, 8 and 24 hours post-infusion. Summary PK parameters for Cycle 1 Day 1 reported.

    Outcome Measure Data

    Analysis Population Description
    All subjects in the FAS who completed at least 1 pharmacokinetic (PK) assessment.
    Arm/Group Title E6201 240 mg/m^2 Weekly E6201 320 mg/m^2 Weekly E6201 160 mg/m^2 Twice Weekly E6201 240 mg/m^2 Twice Weekly E6201 320 mg/m^2 Twice Weekly
    Arm/Group Description Cohort 1: Participants were administered E6201 240 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 2: Participants were administered E6201 320 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 3: Participants were administered E6201 160 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 4: Participants were administered E6201 240 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 5: Participants were administered E6201 320 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose.
    Measure Participants 7 10 3 3 4
    Mean (Standard Deviation) [L]
    523.1
    (76.2)
    940.6
    (52.6)
    718.56
    (57.0)
    536.5
    (73.4)
    523.6
    (42.4)
    14. Secondary Outcome
    Title Number of Participants With Suppression of pERK at 4 Hours Post-dose
    Description phospho-ERK (pERK) in blood assessed by Western blot at 4 hours post-dose
    Time Frame Cycle 1 Day 1, 4 hours post-dose.

    Outcome Measure Data

    Analysis Population Description
    All subjects in the FAS who completed at least 1 PD assessment. Data obtained were not quantitative.
    Arm/Group Title E6201 240 mg/m^2 Weekly E6201 320 mg/m^2 Weekly E6201 160 mg/m^2 Twice Weekly E6201 240 mg/m^2 Twice Weekly E6201 320 mg/m^2 Twice Weekly
    Arm/Group Description E6201 240 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. E6201 320 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. E6201 160 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. E6201 240 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. E6201 320 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose.
    Measure Participants 7 10 3 3 4
    Count of Participants [Participants]
    3
    42.9%
    2
    20%
    2
    66.7%
    2
    66.7%
    1
    25%
    15. Secondary Outcome
    Title Number of Participants With Suppression of pERK at 24 Hours Post-dose
    Description Measurement of phospho-ERK (pERK) in blood assessed by Western blot at 24 hours post-dose
    Time Frame Cycle 1 Day 1, 24 hours post-dose.

    Outcome Measure Data

    Analysis Population Description
    All subjects in the FAS who completed at least 1 PD assessment. Data obtained were not quantitative.
    Arm/Group Title E6201 240 mg/m^2 Weekly E6201 320 mg/m^2 Weekly E6201 160 mg/m^2 Twice Weekly E6201 240 mg/m^2 Twice Weekly E6201 320 mg/m^2 Twice Weekly
    Arm/Group Description Cohort 1: Participants were administered E6201 240 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 2: Participants were administered E6201 320 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 3: Participants were administered E6201 160 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 4: Participants were administered E6201 240 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 5: Participants were administered E6201 320 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose.
    Measure Participants 7 10 3 3 4
    Count of Participants [Participants]
    2
    28.6%
    1
    10%
    2
    66.7%
    1
    33.3%
    0
    0%
    16. Secondary Outcome
    Title Number of Participants With Suppression of pFLT3 at 4 Hours Post-dose
    Description phospho-FLT3 (pFLT3) in blood assessed by Western blot at 4 hours post-dose
    Time Frame Cycle 1 Day 1, 4 hours post-dose.

    Outcome Measure Data

    Analysis Population Description
    All subjects in the FAS who completed at least 1 PD assessment. Data obtained were not quantitative.
    Arm/Group Title E6201 240 mg/m^2 Weekly E6201 320 mg/m^2 Weekly E6201 160 mg/m^2 Twice Weekly E6201 240 mg/m^2 Twice Weekly E6201 320 mg/m^2 Twice Weekly
    Arm/Group Description Cohort 1: Participants were administered E6201 240 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 2: Participants were administered E6201 320 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 3: Participants were administered E6201 160 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 4: Participants were administered E6201 240 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 5: Participants were administered E6201 320 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose.
    Measure Participants 7 10 3 3 4
    Count of Participants [Participants]
    3
    42.9%
    1
    10%
    1
    33.3%
    2
    66.7%
    0
    0%
    17. Secondary Outcome
    Title Number of Participants With Suppression of pFLT3 at 24 Hours Post-dose
    Description phospho-FLT3 (pFLT3) in blood assessed by Western blot at 24 hours post-dose
    Time Frame Cycle 1 Day 1, 24 hours post-dose.

    Outcome Measure Data

    Analysis Population Description
    All subjects in the FAS who completed at least 1 PD assessment. Data obtained were not quantitative.
    Arm/Group Title E6201 240 mg/m^2 Weekly E6201 320 mg/m^2 Weekly E6201 160 mg/m^2 Twice Weekly E6201 240 mg/m^2 Twice Weekly E6201 320 mg/m^2 Twice Weekly
    Arm/Group Description Cohort 1: Participants were administered E6201 240 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 2: Participants were administered E6201 320 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 3: Participants were administered E6201 160 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 4: Participants were administered E6201 240 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 5: Participants were administered E6201 320 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose.
    Measure Participants 7 10 3 3 4
    Count of Participants [Participants]
    0
    0%
    1
    10%
    1
    33.3%
    1
    33.3%
    0
    0%
    18. Secondary Outcome
    Title Number of Participants With Suppression of pAKT at 4 Hours Post-dose
    Description phospho-AKT (pAKT) in blood assessed by Western blot at 4 hours post-dose
    Time Frame Cycle 1 Day 1, 4 hours post-dose.

    Outcome Measure Data

    Analysis Population Description
    All subjects in the FAS who completed at least 1 PD assessment. Data obtained were not quantitative.
    Arm/Group Title E6201 240 mg/m^2 Weekly E6201 320 mg/m^2 Weekly E6201 160 mg/m^2 Twice Weekly E6201 240 mg/m^2 Twice Weekly E6201 320 mg/m^2 Twice Weekly
    Arm/Group Description Cohort 1: Participants were administered E6201 240 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 2: Participants were administered E6201 320 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 3: Participants were administered E6201 160 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 4: Participants were administered E6201 240 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 5: Participants were administered E6201 320 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose.
    Measure Participants 7 10 3 3 4
    Count of Participants [Participants]
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    19. Secondary Outcome
    Title Number of Participants With Suppression of pAKT at 24 Hours Post-dose
    Description phospho-AKT (pAKT) in blood assessed by Western blot at 24 hours post-dose
    Time Frame Cycle 1 Day 1, 24 hours post-dose.

    Outcome Measure Data

    Analysis Population Description
    All subjects in the FAS who completed at least 1 PD assessment. Data obtained were not quantitative.
    Arm/Group Title E6201 240 mg/m^2 Weekly E6201 320 mg/m^2 Weekly E6201 160 mg/m^2 Twice Weekly E6201 240 mg/m^2 Twice Weekly E6201 320 mg/m^2 Twice Weekly
    Arm/Group Description Cohort 1: Participants were administered E6201 240 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 2: Participants were administered E6201 320 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 3: Participants were administered E6201 160 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 4: Participants were administered E6201 240 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 5: Participants were administered E6201 320 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose.
    Measure Participants 7 10 3 3 4
    Count of Participants [Participants]
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    20. Secondary Outcome
    Title Number of Participants With Suppression of pERK by PIA at 4 Hours Post-dose
    Description Blood assay: Plasma inhibitory assay (PIA) measuring pERK in blood at 4 hours post-dose
    Time Frame Cycle 1 Day 1, 4 hours post-dose.

    Outcome Measure Data

    Analysis Population Description
    All subjects in the FAS who completed at least 1 PD assessment. Data obtained were not quantitative.
    Arm/Group Title E6201 240 mg/m^2 Weekly E6201 320 mg/m^2 Weekly E6201 160 mg/m^2 Twice Weekly E6201 240 mg/m^2 Twice Weekly E6201 320 mg/m^2 Twice Weekly
    Arm/Group Description Cohort 1: Participants were administered E6201 240 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 2: Participants were administered E6201 320 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 3: Participants were administered E6201 160 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 4: Participants were administered E6201 240 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 5: Participants were administered E6201 320 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose.
    Measure Participants 7 10 3 3 4
    Count of Participants [Participants]
    7
    100%
    5
    50%
    2
    66.7%
    3
    100%
    2
    50%
    21. Secondary Outcome
    Title Number of Participants With Suppression of in pERK by PIA 24 Hours Post-dose
    Description Blood assay: Plasma inhibitory assay (PIA) measuring pERK in blood at 24 hours post-dose
    Time Frame Cycle 1 Day 1, 24 hours post-dose.

    Outcome Measure Data

    Analysis Population Description
    All subjects in the FAS who completed at least 1 PD assessment. Data obtained were not quantitative.
    Arm/Group Title E6201 240 mg/m^2 Weekly E6201 320 mg/m^2 Weekly E6201 160 mg/m^2 Twice Weekly E6201 240 mg/m^2 Twice Weekly E6201 320 mg/m^2 Twice Weekly
    Arm/Group Description Cohort 1: Participants were administered E6201 240 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 2: Participants were administered E6201 320 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 3: Participants were administered E6201 160 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 4: Participants were administered E6201 240 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 5: Participants were administered E6201 320 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose.
    Measure Participants 7 10 3 3 4
    Count of Participants [Participants]
    1
    14.3%
    2
    20%
    1
    33.3%
    0
    0%
    1
    25%
    22. Secondary Outcome
    Title Number of Participants With Suppression of pFLT3 by PIA at 4 Hours Post-dose
    Description Blood assay: Plasma inhibitory assay (PIA) measuring pFLT3 in blood at 4 hours post-dose
    Time Frame Cycle 1 Day 1, 4 hours post-dose.

    Outcome Measure Data

    Analysis Population Description
    All subjects in the FAS who completed at least 1 PD assessment. Data obtained were not quantitative.
    Arm/Group Title E6201 240 mg/m^2 Weekly E6201 320 mg/m^2 Weekly E6201 160 mg/m^2 Twice Weekly E6201 240 mg/m^2 Twice Weekly E6201 320 mg/m^2 Twice Weekly
    Arm/Group Description Cohort 1: Participants were administered E6201 240 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 2: Participants were administered E6201 320 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 3: Participants were administered E6201 160 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 4: Participants were administered E6201 240 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 5: Participants were administered E6201 320 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose.
    Measure Participants 7 10 3 3 4
    Count of Participants [Participants]
    6
    85.7%
    5
    50%
    2
    66.7%
    3
    100%
    2
    50%
    23. Secondary Outcome
    Title Number of Participants With Suppression of pFLT3 by PIA at 24 Hours Post-dose
    Description Blood assay: Plasma inhibitory assay (PIA) measuring pFLT3 in blood at 24 hours post-dose
    Time Frame Cycle 1 Day 1, 24 hours post-dose.

    Outcome Measure Data

    Analysis Population Description
    All subjects in the FAS who completed at least 1 PD assessment. Data obtained were not quantitative.
    Arm/Group Title E6201 240 mg/m^2 Weekly E6201 320 mg/m^2 Weekly E6201 160 mg/m^2 Twice Weekly E6201 240 mg/m^2 Twice Weekly E6201 320 mg/m^2 Twice Weekly
    Arm/Group Description Cohort 1: Participants were administered E6201 240 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 2: Participants were administered E6201 320 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 3: Participants were administered E6201 160 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 4: Participants were administered E6201 240 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. Cohort 5: Participants were administered E6201 320 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose.
    Measure Participants 7 10 3 3 4
    Count of Participants [Participants]
    1
    14.3%
    2
    20%
    1
    33.3%
    0
    0%
    1
    25%

    Adverse Events

    Time Frame Adverse event data were collected for each subject from C1D1 to 6 months after the last dose of study drug. The total duration of the study was 26 months.
    Adverse Event Reporting Description Adverse events were reported for all study participants who were administered any fraction of a dose of study medication.
    Arm/Group Title E6201 240 mg/m^2 Weekly E6201 320 mg/m^2 Weekly E6201 160 mg/m^2 Twice Weekly E6201 240 mg/m^2 Twice Weekly E6201 320 mg/m^2 Twice Weekly
    Arm/Group Description E6201 240 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. E6201 320 mg/m^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. E6201 160 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. E6201 240 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose. E6201 320 mg/m^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for discontinuation of study drug, and followed for up to 6 months after the last dose.
    All Cause Mortality
    E6201 240 mg/m^2 Weekly E6201 320 mg/m^2 Weekly E6201 160 mg/m^2 Twice Weekly E6201 240 mg/m^2 Twice Weekly E6201 320 mg/m^2 Twice Weekly
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/7 (42.9%) 4/10 (40%) 1/3 (33.3%) 0/3 (0%) 1/4 (25%)
    Serious Adverse Events
    E6201 240 mg/m^2 Weekly E6201 320 mg/m^2 Weekly E6201 160 mg/m^2 Twice Weekly E6201 240 mg/m^2 Twice Weekly E6201 320 mg/m^2 Twice Weekly
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/7 (57.1%) 10/10 (100%) 3/3 (100%) 2/3 (66.7%) 2/4 (50%)
    Blood and lymphatic system disorders
    Febrile neutropenia 0/7 (0%) 1/10 (10%) 1 0/3 (0%) 1 1/3 (33.3%) 3 0/4 (0%) 3
    Gastrointestinal disorders
    GI hemorrhage 1/7 (14.3%) 1 0/10 (0%) 1 0/3 (0%) 1 0/3 (0%) 1 0/4 (0%) 1
    General disorders
    Multi-organ failure 1/7 (14.3%) 1 0/10 (0%) 1 0/3 (0%) 1 0/3 (0%) 1 0/4 (0%) 1
    Non-cardiac chest pain 0/7 (0%) 0/10 (0%) 1/3 (33.3%) 1 0/3 (0%) 1 0/4 (0%) 1
    Asthenia 0/7 (0%) 0/10 (0%) 0/3 (0%) 0/3 (0%) 1/4 (25%) 1
    Infections and infestations
    Cellulitis 1/7 (14.3%) 1 2/10 (20%) 2 0/3 (0%) 2 0/3 (0%) 2 0/4 (0%) 2
    Pneumonia 1/7 (14.3%) 1 0/10 (0%) 1 0/3 (0%) 1 0/3 (0%) 1 0/4 (0%) 1
    Sepsis 1/7 (14.3%) 1 3/10 (30%) 3 1/3 (33.3%) 1 1/3 (33.3%) 1 1/4 (25%) 1
    Alpha hemolytic Strep infection 1/7 (14.3%) 1 0/10 (0%) 1 0/3 (0%) 1 0/3 (0%) 1 0/4 (0%) 1
    Pseudomonal bateremia 0/7 (0%) 1/10 (10%) 1 0/3 (0%) 1 0/3 (0%) 1 0/4 (0%) 1
    Klebsiella bacteremia 0/7 (0%) 1/10 (10%) 2 0/3 (0%) 2 0/3 (0%) 2 0/4 (0%) 2
    Respiratory tract infection fungal 0/7 (0%) 1/10 (10%) 1 0/3 (0%) 1 0/3 (0%) 1 0/4 (0%) 1
    Pneumonia 0/7 (0%) 3/10 (30%) 7 0/3 (0%) 7 0/3 (0%) 7 0/4 (0%) 7
    Epiglottitis 0/7 (0%) 0/10 (0%) 1/3 (33.3%) 1 0/3 (0%) 1 0/4 (0%) 1
    Pyelonephritis 0/7 (0%) 0/10 (0%) 1/3 (33.3%) 1 0/3 (0%) 1 0/4 (0%) 1
    Perirectal abscess 0/7 (0%) 0/10 (0%) 0/3 (0%) 1/3 (33.3%) 1 0/4 (0%) 1
    Sinusitis 0/7 (0%) 0/10 (0%) 0/3 (0%) 1/3 (33.3%) 1 0/4 (0%) 1
    Lobar pneumonia 0/7 (0%) 0/10 (0%) 0/3 (0%) 0/3 (0%) 1/4 (25%) 1
    Investigations
    ECG QTc prolonged 0/7 (0%) 1/10 (10%) 1 0/3 (0%) 1 0/3 (0%) 1 0/4 (0%) 1
    Metabolism and nutrition disorders
    Tumor lysis syndrome 1/7 (14.3%) 1 0/10 (0%) 1 0/3 (0%) 1 0/3 (0%) 1 0/4 (0%) 1
    Nervous system disorders
    Intracranial hemorrhage 0/7 (0%) 2/10 (20%) 2 0/3 (0%) 2 0/3 (0%) 2 0/4 (0%) 2
    Respiratory, thoracic and mediastinal disorders
    Dyspnea 0/7 (0%) 1/10 (10%) 1 1/3 (33.3%) 1 0/3 (0%) 1 0/4 (0%) 1
    Other (Not Including Serious) Adverse Events
    E6201 240 mg/m^2 Weekly E6201 320 mg/m^2 Weekly E6201 160 mg/m^2 Twice Weekly E6201 240 mg/m^2 Twice Weekly E6201 320 mg/m^2 Twice Weekly
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 7/7 (100%) 10/10 (100%) 3/3 (100%) 3/3 (100%) 4/4 (100%)
    Blood and lymphatic system disorders
    Febrile neutropenia 1/7 (14.3%) 3/10 (30%) 0/3 (0%) 2/3 (66.7%) 1/4 (25%)
    Leucocytosis 1/7 (14.3%) 3/10 (30%) 0/3 (0%) 1/3 (33.3%) 0/4 (0%)
    Spleen disorder 1/7 (14.3%) 2/10 (20%) 0/3 (0%) 0/3 (0%) 0/4 (0%)
    Gastrointestinal disorders
    Abdominal distension 0/7 (0%) 1/10 (10%) 0/3 (0%) 0/3 (0%) 1/4 (25%)
    Abdominal pain 2/7 (28.6%) 0/10 (0%) 0/3 (0%) 1/3 (33.3%) 0/4 (0%)
    Diarrhea 2/7 (28.6%) 1/10 (10%) 0/3 (0%) 1/3 (33.3%) 0/4 (0%)
    Dry mouth 0/7 (0%) 0/10 (0%) 0/3 (0%) 2/3 (66.7%) 1/4 (25%)
    Nausea 2/7 (28.6%) 2/10 (20%) 0/3 (0%) 1/3 (33.3%) 0/4 (0%)
    Proctalgia 0/7 (0%) 1/10 (10%) 0/3 (0%) 1/3 (33.3%) 0/4 (0%)
    Stomatitis 1/7 (14.3%) 2/10 (20%) 0/3 (0%) 1/3 (33.3%) 0/4 (0%)
    General disorders
    Chills 0/7 (0%) 0/10 (0%) 1/3 (33.3%) 1/3 (33.3%) 0/4 (0%)
    Fatigue 1/7 (14.3%) 2/10 (20%) 1/3 (33.3%) 1/3 (33.3%) 2/4 (50%)
    Non-cardiac chest pain 0/7 (0%) 1/10 (10%) 1/3 (33.3%) 0/3 (0%) 0/4 (0%)
    Pyrexia 0/7 (0%) 1/10 (10%) 0/3 (0%) 1/3 (33.3%) 0/4 (0%)
    Infections and infestations
    Cellulitis 1/7 (14.3%) 2/10 (20%) 1/3 (33.3%) 0/3 (0%) 0/4 (0%)
    Diverticulitis 0/7 (0%) 0/10 (0%) 1/3 (33.3%) 1/3 (33.3%) 0/4 (0%)
    Pneumonia 1/7 (14.3%) 3/10 (30%) 0/3 (0%) 0/3 (0%) 0/4 (0%)
    Pneumonia fungal 1/7 (14.3%) 1/10 (10%) 0/3 (0%) 0/3 (0%) 0/4 (0%)
    Sepsis 1/7 (14.3%) 3/10 (30%) 1/3 (33.3%) 1/3 (33.3%) 1/4 (25%)
    Upper respiratory tract infection 0/7 (0%) 2/10 (20%) 0/3 (0%) 0/3 (0%) 0/4 (0%)
    Urinary tract infection 0/7 (0%) 2/10 (20%) 0/3 (0%) 0/3 (0%) 0/4 (0%)
    Injury, poisoning and procedural complications
    Fall 1/7 (14.3%) 1/10 (10%) 1/3 (33.3%) 0/3 (0%) 0/4 (0%)
    Investigations
    ALT increased 1/7 (14.3%) 0/10 (0%) 1/3 (33.3%) 2/3 (66.7%) 0/4 (0%)
    AST increased 1/7 (14.3%) 0/10 (0%) 1/3 (33.3%) 1/3 (33.3%) 1/4 (25%)
    ECG QT prolonged 1/7 (14.3%) 1/10 (10%) 0/3 (0%) 0/3 (0%) 0/4 (0%)
    Metabolism and nutrition disorders
    Decreased appetite 1/7 (14.3%) 2/10 (20%) 0/3 (0%) 1/3 (33.3%) 1/4 (25%)
    Dehydration 0/7 (0%) 0/10 (0%) 0/3 (0%) 1/3 (33.3%) 1/4 (25%)
    Fluid overload 0/7 (0%) 1/10 (10%) 0/3 (0%) 0/3 (0%) 1/4 (25%)
    Hypokalemia 1/7 (14.3%) 0/10 (0%) 0/3 (0%) 0/3 (0%) 1/4 (25%)
    Musculoskeletal and connective tissue disorders
    Muscular weakness 1/7 (14.3%) 1/10 (10%) 1/3 (33.3%) 0/3 (0%) 0/4 (0%)
    Nervous system disorders
    Dizziness 0/7 (0%) 0/10 (0%) 1/3 (33.3%) 1/3 (33.3%) 1/4 (25%)
    Hemorrhage intracranial 0/7 (0%) 2/10 (20%) 0/3 (0%) 0/3 (0%) 0/4 (0%)
    Psychiatric disorders
    Confusional state 0/7 (0%) 2/10 (20%) 1/3 (33.3%) 0/3 (0%) 1/4 (25%)
    Mental disorder 2/7 (28.6%) 0/10 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%)
    Renal and urinary disorders
    Hematuria 0/7 (0%) 1/10 (10%) 0/3 (0%) 0/3 (0%) 1/4 (25%)
    Pollakiuria 1/7 (14.3%) 0/10 (0%) 0/3 (0%) 0/3 (0%) 1/4 (25%)
    Urinary retention 0/7 (0%) 2/10 (20%) 1/3 (33.3%) 0/3 (0%) 0/4 (0%)
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure 1/7 (14.3%) 1/10 (10%) 0/3 (0%) 0/3 (0%) 0/4 (0%)
    Cough 1/7 (14.3%) 1/10 (10%) 1/3 (33.3%) 0/3 (0%) 2/4 (50%)
    Dyspnea 1/7 (14.3%) 2/10 (20%) 2/3 (66.7%) 0/3 (0%) 1/4 (25%)
    Nasal congestion 1/7 (14.3%) 1/10 (10%) 0/3 (0%) 0/3 (0%) 1/4 (25%)
    Oropharyngeal pain 1/7 (14.3%) 0/10 (0%) 1/3 (33.3%) 0/3 (0%) 1/4 (25%)
    Skin and subcutaneous tissue disorders
    Pruritis 1/7 (14.3%) 0/10 (0%) 0/3 (0%) 1/3 (33.3%) 0/4 (0%)
    Rash 0/7 (0%) 0/10 (0%) 0/3 (0%) 2/3 (66.7%) 0/4 (0%)
    Rash maculo-papular 1/7 (14.3%) 2/10 (20%) 0/3 (0%) 0/3 (0%) 0/4 (0%)
    Skin lesion 0/7 (0%) 1/10 (10%) 1/3 (33.3%) 0/3 (0%) 0/4 (0%)
    Vascular disorders
    Hypotension 0/7 (0%) 2/10 (20%) 1/3 (33.3%) 1/3 (33.3%) 0/4 (0%)

    Limitations/Caveats

    Although E6201 exhibited an acceptable safety profile when administered at doses up to the MTD of 320 mg/m^2 IV twice weekly, insufficient efficacy was observed during the Phase 1 portion of the study. Thus, the Phase 2a portion was not initiated.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Chief Development Officer
    Organization Spirita Oncology, LLC
    Phone +1 (713) 898-8965
    Email linda.paradiso@spiritaoncology.com
    Responsible Party:
    Spirita Oncology, LLC
    ClinicalTrials.gov Identifier:
    NCT02418000
    Other Study ID Numbers:
    • BSC-101-01
    First Posted:
    Apr 16, 2015
    Last Update Posted:
    Mar 20, 2019
    Last Verified:
    Mar 1, 2019