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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02418000
Recruitment Status : Terminated (Insufficient efficacy in Phase 1 dose-escalation portion of study)
First Posted : April 16, 2015
Results First Posted : March 5, 2019
Last Update Posted : March 20, 2019
Sponsor:
Information provided by (Responsible Party):
Spirita Oncology, LLC

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Sequential Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions AML
MDS
CMML
Intervention Drug: E6201
Enrollment 27
Recruitment Details  
Pre-assignment Details  
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
Hide 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
Reason Not Completed
Withdrawal by Subject             2             0             0             0             0
Lack of Efficacy             4             0             0             0             0
Prepare for HSCT             1             0             0             0             0
Period Title: Cohort 2: E6201 320 mg/m^2 Weekly
Started 0 10 0 0 0
Completed 0 0 0 0 0
Not Completed 0 10 0 0 0
Reason Not Completed
Withdrawal by Subject             0             1             0             0             0
Lack of Efficacy             0             9             0             0             0
Period Title: Cohort 3: 160 mg/m^2 Twice Weekly
Started 0 0 3 0 0
Completed 0 0 0 0 0
Not Completed 0 0 3 0 0
Reason Not Completed
Lack of Efficacy             0             0             3             0             0
Period Title: Cohort 4: 240 mg/m^2 Twice Weekly
Started 0 0 0 3 0
Completed 0 0 0 0 0
Not Completed 0 0 0 3 0
Reason Not Completed
Lack of Efficacy             0             0             0             3             0
Period Title: Cohort 5: 320 mg/m^2 Twice Weekly
Started 0 0 0 0 4
Completed 0 0 0 0 0
Not Completed 0 0 0 0 4
Reason Not Completed
Withdrawal by Subject             0             0             0             0             1
Lack of Efficacy             0             0             0             0             3
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
Hide 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 Number of Baseline Participants 7 10 3 3 4 27
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 7 participants 10 participants 3 participants 3 participants 4 participants 27 participants
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  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 10 participants 3 participants 3 participants 4 participants 27 participants
Female
5
  71.4%
4
  40.0%
2
  66.7%
1
  33.3%
2
  50.0%
14
  51.9%
Male
2
  28.6%
6
  60.0%
1
  33.3%
2
  66.7%
2
  50.0%
13
  48.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 10 participants 3 participants 3 participants 4 participants 27 participants
Hispanic or Latino
1
  14.3%
1
  10.0%
1
  33.3%
0
   0.0%
0
   0.0%
3
  11.1%
Not Hispanic or Latino
4
  57.1%
8
  80.0%
2
  66.7%
3
 100.0%
4
 100.0%
21
  77.8%
Unknown or Not Reported
2
  28.6%
1
  10.0%
0
   0.0%
0
   0.0%
0
   0.0%
3
  11.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 10 participants 3 participants 3 participants 4 participants 27 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
1
  33.3%
1
  25.0%
2
   7.4%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
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
   0.0%
0
   0.0%
4
  14.8%
White
5
  71.4%
6
  60.0%
3
 100.0%
2
  66.7%
3
  75.0%
19
  70.4%
More than one race
1
  14.3%
1
  10.0%
0
   0.0%
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%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 7 participants 10 participants 3 participants 3 participants 4 participants 27 participants
7 10 3 3 4 27
Disease Type  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 10 participants 3 participants 3 participants 4 participants 27 participants
AML
4
  57.1%
10
 100.0%
3
 100.0%
3
 100.0%
4
 100.0%
24
  88.9%
MDS
1
  14.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   3.7%
CMML
2
  28.6%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
   7.4%
Eastern Cooperative Group (ECOG) Performance Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 10 participants 3 participants 3 participants 4 participants 27 participants
0
2
  28.6%
1
  10.0%
0
   0.0%
0
   0.0%
0
   0.0%
3
  11.1%
1
5
  71.4%
6
  60.0%
2
  66.7%
3
 100.0%
4
 100.0%
20
  74.1%
2
0
   0.0%
3
  30.0%
1
  33.3%
0
   0.0%
0
   0.0%
4
  14.8%
3
0
   0.0%
0
   0.0%
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%
0
   0.0%
0
   0.0%
[1]
Measure Description:

ECOG Performance Status:

0 = Fully active, able to carry on all pre-disease performance without restriction

  1. = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work
  2. = Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours
  3. = Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours
  4. = Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair
  5. = Dead
Prior Cancer Therapies  
Median (Full Range)
Unit of measure:  Number of treatment regimens
 Number Analyzed 7 participants 10 participants 3 participants 3 participants 4 participants 27 participants
All Prior Cancer Treatment Regimens
3
(2 to 8)
6.5
(4 to 14)
4
(4 to 7)
5
(4 to 10)
4
(4 to 11)
5
(2 to 14)
Prior FLT3 Inhibitor Treatment Regimens
1
(1 to 1)
1
(1 to 3)
1
(1 to 1)
1
(1 to 1)
1
(1 to 1)
1
(1 to 3)
1.Primary Outcome
Title Maximum Tolerated Dose (MTD) of E6201
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 27
Measure Type: Number
Unit of Measure: E6201 MTD (mg/m^2) IV twice weekly
320
2.Primary Outcome
Title Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 7 10 3 3 4
Measure Type: Number
Unit of Measure: Number of Participants with DLTs
1 1 0 0 0
3.Secondary Outcome
Title Overall Response Rate
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 7 10 3 3 4
Measure Type: Number
Unit of Measure: Objective Responses
0 0 0 0 0
4.Secondary Outcome
Title Duration of Response
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Progression-Free Survival
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title Overall Survival
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 3 9 2 2 3
Median (Standard Deviation)
Unit of Measure: 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
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 7 10 3 3 4
Mean (Standard Deviation)
Unit of Measure: 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
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 7 10 3 3 4
Mean (Standard Deviation)
Unit of Measure: 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
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 7 10 3 3 4
Mean (Standard Deviation)
Unit of Measure: 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
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 7 10 3 3 4
Mean (Standard Deviation)
Unit of Measure: 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
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 7 10 3 3 4
Mean (Standard Deviation)
Unit of Measure: 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
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 7 10 3 3 4
Mean (Standard Deviation)
Unit of Measure: 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
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 7 10 3 3 4
Mean (Standard Deviation)
Unit of Measure: 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
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 7 10 3 3 4
Measure Type: Count of Participants
Unit of Measure: Participants
3
  42.9%
2
  20.0%
2
  66.7%
2
  66.7%
1
  25.0%
15.Secondary Outcome
Title Number of Participants With Suppression of pERK at 24 Hours Post-dose
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 7 10 3 3 4
Measure Type: Count of Participants
Unit of Measure: Participants
2
  28.6%
1
  10.0%
2
  66.7%
1
  33.3%
0
   0.0%
16.Secondary Outcome
Title Number of Participants With Suppression of pFLT3 at 4 Hours Post-dose
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 7 10 3 3 4
Measure Type: Count of Participants
Unit of Measure: Participants
3
  42.9%
1
  10.0%
1
  33.3%
2
  66.7%
0
   0.0%
17.Secondary Outcome
Title Number of Participants With Suppression of pFLT3 at 24 Hours Post-dose
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 7 10 3 3 4
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
1
  10.0%
1
  33.3%
1
  33.3%
0
   0.0%
18.Secondary Outcome
Title Number of Participants With Suppression of pAKT at 4 Hours Post-dose
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 7 10 3 3 4
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
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
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 7 10 3 3 4
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
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
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 7 10 3 3 4
Measure Type: Count of Participants
Unit of Measure: Participants
7
 100.0%
5
  50.0%
2
  66.7%
3
 100.0%
2
  50.0%
21.Secondary Outcome
Title Number of Participants With Suppression of in pERK by PIA 24 Hours Post-dose
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 7 10 3 3 4
Measure Type: Count of Participants
Unit of Measure: Participants
1
  14.3%
2
  20.0%
1
  33.3%
0
   0.0%
1
  25.0%
22.Secondary Outcome
Title Number of Participants With Suppression of pFLT3 by PIA at 4 Hours Post-dose
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 7 10 3 3 4
Measure Type: Count of Participants
Unit of Measure: Participants
6
  85.7%
5
  50.0%
2
  66.7%
3
 100.0%
2
  50.0%
23.Secondary Outcome
Title Number of Participants With Suppression of pFLT3 by PIA at 24 Hours Post-dose
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 7 10 3 3 4
Measure Type: Count of Participants
Unit of Measure: Participants
1
  14.3%
2
  20.0%
1
  33.3%
0
   0.0%
1
  25.0%
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
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/7 (42.86%)      4/10 (40.00%)      1/3 (33.33%)      0/3 (0.00%)      1/4 (25.00%)    
Hide 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 (57.14%)      10/10 (100.00%)      3/3 (100.00%)      2/3 (66.67%)      2/4 (50.00%)    
Blood and lymphatic system disorders           
Febrile neutropenia † 1  0/7 (0.00%)  1/10 (10.00%)  1 0/3 (0.00%)  1/3 (33.33%)  3 0/4 (0.00%) 
Gastrointestinal disorders           
GI hemorrhage † 1  1/7 (14.29%)  1 0/10 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
General disorders           
Multi-organ failure † 1  1/7 (14.29%)  1 0/10 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Non-cardiac chest pain † 1  0/7 (0.00%)  0/10 (0.00%)  1/3 (33.33%)  1 0/3 (0.00%)  0/4 (0.00%) 
Asthenia † 1  0/7 (0.00%)  0/10 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  1
Infections and infestations           
Cellulitis † 1  1/7 (14.29%)  1 2/10 (20.00%)  2 0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Pneumonia † 1  1/7 (14.29%)  1 0/10 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Sepsis † 1  1/7 (14.29%)  1 3/10 (30.00%)  3 1/3 (33.33%)  1 1/3 (33.33%)  1/4 (25.00%)  1
Alpha hemolytic Strep infection † 1  1/7 (14.29%)  1 0/10 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Pseudomonal bateremia † 1  0/7 (0.00%)  1/10 (10.00%)  1 0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Klebsiella bacteremia † 1  0/7 (0.00%)  1/10 (10.00%)  2 0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Respiratory tract infection fungal † 1  0/7 (0.00%)  1/10 (10.00%)  1 0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Pneumonia † 1  0/7 (0.00%)  3/10 (30.00%)  7 0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Epiglottitis † 1  0/7 (0.00%)  0/10 (0.00%)  1/3 (33.33%)  1 0/3 (0.00%)  0/4 (0.00%) 
Pyelonephritis † 1  0/7 (0.00%)  0/10 (0.00%)  1/3 (33.33%)  1 0/3 (0.00%)  0/4 (0.00%) 
Perirectal abscess † 1  0/7 (0.00%)  0/10 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  1 0/4 (0.00%) 
Sinusitis † 1  0/7 (0.00%)  0/10 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  1 0/4 (0.00%) 
Lobar pneumonia † 1  0/7 (0.00%)  0/10 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%)  1
Investigations           
ECG QTc prolonged † 1  0/7 (0.00%)  1/10 (10.00%)  1 0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Metabolism and nutrition disorders           
Tumor lysis syndrome † 1  1/7 (14.29%)  1 0/10 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Nervous system disorders           
Intracranial hemorrhage † 1  0/7 (0.00%)  2/10 (20.00%)  2 0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Dyspnea † 1  0/7 (0.00%)  1/10 (10.00%)  1 1/3 (33.33%)  1 0/3 (0.00%)  0/4 (0.00%) 
1
Term from vocabulary, MedDRA (15.0)
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 4%
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 (100.00%)      10/10 (100.00%)      3/3 (100.00%)      3/3 (100.00%)      4/4 (100.00%)    
Blood and lymphatic system disorders           
Febrile neutropenia † 1  1/7 (14.29%)  3/10 (30.00%)  0/3 (0.00%)  2/3 (66.67%)  1/4 (25.00%) 
Leucocytosis † 1  1/7 (14.29%)  3/10 (30.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%) 
Spleen disorder † 1  1/7 (14.29%)  2/10 (20.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Gastrointestinal disorders           
Abdominal distension † 1  0/7 (0.00%)  1/10 (10.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%) 
Abdominal pain † 1  2/7 (28.57%)  0/10 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%) 
Diarrhea † 1  2/7 (28.57%)  1/10 (10.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%) 
Dry mouth † 1  0/7 (0.00%)  0/10 (0.00%)  0/3 (0.00%)  2/3 (66.67%)  1/4 (25.00%) 
Nausea † 1  2/7 (28.57%)  2/10 (20.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%) 
Proctalgia † 1  0/7 (0.00%)  1/10 (10.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%) 
Stomatitis † 1  1/7 (14.29%)  2/10 (20.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%) 
General disorders           
Chills † 1  0/7 (0.00%)  0/10 (0.00%)  1/3 (33.33%)  1/3 (33.33%)  0/4 (0.00%) 
Fatigue † 1  1/7 (14.29%)  2/10 (20.00%)  1/3 (33.33%)  1/3 (33.33%)  2/4 (50.00%) 
Non-cardiac chest pain † 1  0/7 (0.00%)  1/10 (10.00%)  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%) 
Pyrexia † 1  0/7 (0.00%)  1/10 (10.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%) 
Infections and infestations           
Cellulitis † 1  1/7 (14.29%)  2/10 (20.00%)  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%) 
Diverticulitis † 1  0/7 (0.00%)  0/10 (0.00%)  1/3 (33.33%)  1/3 (33.33%)  0/4 (0.00%) 
Pneumonia † 1  1/7 (14.29%)  3/10 (30.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Pneumonia fungal † 1  1/7 (14.29%)  1/10 (10.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Sepsis † 1  1/7 (14.29%)  3/10 (30.00%)  1/3 (33.33%)  1/3 (33.33%)  1/4 (25.00%) 
Upper respiratory tract infection † 1  0/7 (0.00%)  2/10 (20.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Urinary tract infection † 1  0/7 (0.00%)  2/10 (20.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Injury, poisoning and procedural complications           
Fall † 1  1/7 (14.29%)  1/10 (10.00%)  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%) 
Investigations           
ALT increased † 1  1/7 (14.29%)  0/10 (0.00%)  1/3 (33.33%)  2/3 (66.67%)  0/4 (0.00%) 
AST increased † 1  1/7 (14.29%)  0/10 (0.00%)  1/3 (33.33%)  1/3 (33.33%)  1/4 (25.00%) 
ECG QT prolonged † 1  1/7 (14.29%)  1/10 (10.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Metabolism and nutrition disorders           
Decreased appetite † 1  1/7 (14.29%)  2/10 (20.00%)  0/3 (0.00%)  1/3 (33.33%)  1/4 (25.00%) 
Dehydration † 1  0/7 (0.00%)  0/10 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  1/4 (25.00%) 
Fluid overload † 1  0/7 (0.00%)  1/10 (10.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%) 
Hypokalemia † 1  1/7 (14.29%)  0/10 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%) 
Musculoskeletal and connective tissue disorders           
Muscular weakness † 1  1/7 (14.29%)  1/10 (10.00%)  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%) 
Nervous system disorders           
Dizziness † 1  0/7 (0.00%)  0/10 (0.00%)  1/3 (33.33%)  1/3 (33.33%)  1/4 (25.00%) 
Hemorrhage intracranial † 1  0/7 (0.00%)  2/10 (20.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Psychiatric disorders           
Confusional state † 1  0/7 (0.00%)  2/10 (20.00%)  1/3 (33.33%)  0/3 (0.00%)  1/4 (25.00%) 
Mental disorder † 1  2/7 (28.57%)  0/10 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Renal and urinary disorders           
Hematuria † 1  0/7 (0.00%)  1/10 (10.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%) 
Pollakiuria † 1  1/7 (14.29%)  0/10 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%) 
Urinary retention † 1  0/7 (0.00%)  2/10 (20.00%)  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Acute respiratory failure † 1  1/7 (14.29%)  1/10 (10.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Cough † 1  1/7 (14.29%)  1/10 (10.00%)  1/3 (33.33%)  0/3 (0.00%)  2/4 (50.00%) 
Dyspnea † 1  1/7 (14.29%)  2/10 (20.00%)  2/3 (66.67%)  0/3 (0.00%)  1/4 (25.00%) 
Nasal congestion † 1  1/7 (14.29%)  1/10 (10.00%)  0/3 (0.00%)  0/3 (0.00%)  1/4 (25.00%) 
Oropharyngeal pain † 1  1/7 (14.29%)  0/10 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  1/4 (25.00%) 
Skin and subcutaneous tissue disorders           
Pruritis † 1  1/7 (14.29%)  0/10 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/4 (0.00%) 
Rash † 1  0/7 (0.00%)  0/10 (0.00%)  0/3 (0.00%)  2/3 (66.67%)  0/4 (0.00%) 
Rash maculo-papular † 1  1/7 (14.29%)  2/10 (20.00%)  0/3 (0.00%)  0/3 (0.00%)  0/4 (0.00%) 
Skin lesion † 1  0/7 (0.00%)  1/10 (10.00%)  1/3 (33.33%)  0/3 (0.00%)  0/4 (0.00%) 
Vascular disorders           
Hypotension † 1  0/7 (0.00%)  2/10 (20.00%)  1/3 (33.33%)  1/3 (33.33%)  0/4 (0.00%) 
1
Term from vocabulary, MedDRA (15.0)
†
Indicates events were collected by systematic assessment
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.
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
Layout table for Results Point of Contact information
Name/Title: Chief Development Officer
Organization: Spirita Oncology, LLC
Phone: +1 (713) 898-8965
EMail: linda.paradiso@spiritaoncology.com
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Responsible Party: Spirita Oncology, LLC
ClinicalTrials.gov Identifier: NCT02418000    
Other Study ID Numbers: BSC-101-01
First Submitted: February 18, 2015
First Posted: April 16, 2015
Results First Submitted: November 8, 2018
Results First Posted: March 5, 2019
Last Update Posted: March 20, 2019