AMLPhase 1/2NCT02418000
A Study of E6201 for the Treatment of Advanced Hematologic Malignancies With FLT3 and/or Ras Mutations
A Phase 1/2 study testing E6201 in people with AML and MDS, run by Spirita Oncology, LLC at 4 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- What is being tested?
- E6201
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 4 sitesUnited States
- Study dates
- 10 Apr 2015to 8 Jun 2017
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Colorado Blood Cancer Institute
Denver, Colorado, 80218
MD Anderson Cancer Center
Houston, Texas, 77030
Texas Transplant Institute
San Antonio, Texas, 78229
H. Lee Moffitt Cancer Center & research Institute
Tampa, Florida, 33612
About this study
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)
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.
Read the 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.
- Being tested
- E6201
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
E6201Drug
Also called Dual inhibitor of FLT3 and MEK1
Single Group Assignment
| Study group | Role | What they receive |
|---|---|---|
| E6201 240 mg/m^2 IV weekly | Experimental | 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) Receives: Drug: E6201 |
| E6201 320 mg/m^2 IV weekly | Experimental | 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) Receives: Drug: E6201 |
| E6201 160 mg/m^2 IV twice weekly | Experimental | 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) Receives: Drug: E6201 |
| E6201 240 mg/m^2 IV twice weekly | Experimental | 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) Receives: Drug: E6201 |
| E6201 320 mg/m^2 IV twice weekly | Experimental | 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) Receives: Drug: E6201 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of E6201
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.
Measured: Up to 6 weeks for each dose cohort
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
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.
Measured: Up to 6 weeks for each dose cohort
Secondary outcomes (21)
Overall Response Rate
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%.
Measured: At the end of C1 and every 2 cycles thereafter through 6 months following last dose of study drug
Duration of Response
Length of time from the first evidence of objective response to the first evidence of progression
Measured: At the end of C1 and every 2 cycles thereafter through 6 months following last dose of study drug
Progression-Free Survival
Length of time from the date of first administration of study drug to the first evidence of disease progression or death, whichever is earlier
Measured: From Cycle 1 Day 1 (C1D1) until death or study closure, up to 26 months
Overall Survival
Length of time from the date of first administration of study drug to the date of death from any cause
Measured: From C1D1 until death or study closure, up to 26 months
Pharmacokinetic Profile of E6201 in Plasma: Cmax
Cmax: Maximum measured plasma concentration over the collection period
Measured: 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.
Pharmacokinetics of E6201 in Plasma: Tmax
Tmax: Time to maximum measured plasma concentration
Measured: 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.
Pharmacokinetic Profile of E6201 in Plasma: AUCT
Area under the plasma concentration versus time curve (AUC) to the last measurable concentration over the sampling time-interval.
Measured: 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.
Pharmacokinetic Profile of E6201 in Plasma: AUCI
AUCI: The area under the concentration versus time curve from time 0 to infinity
Measured: 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.
Pharmacokinetic Profile of E6201 in Plasma: T1/2
T1/2: The apparent first-order elimination half-life
Measured: 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.
Pharmacokinetic Profile of E6201 in Plasma: CLobs
Clearance observed (CLobs): Total body clearance for extravascular administration
Measured: 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.
Pharmacokinetic Profile of E6201 in Plasma: VDobs
Measurement of apparent volume of distribution observed (VDobs)
Measured: 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.
Number of Participants With Suppression of pERK at 4 Hours Post-dose
phospho-ERK (pERK) in blood assessed by Western blot at 4 hours post-dose
Measured: Cycle 1 Day 1, 4 hours post-dose.
Number of Participants With Suppression of pERK at 24 Hours Post-dose
Measurement of phospho-ERK (pERK) in blood assessed by Western blot at 24 hours post-dose
Measured: Cycle 1 Day 1, 24 hours post-dose.
Number of Participants With Suppression of pFLT3 at 4 Hours Post-dose
phospho-FLT3 (pFLT3) in blood assessed by Western blot at 4 hours post-dose
Measured: Cycle 1 Day 1, 4 hours post-dose.
Number of Participants With Suppression of pFLT3 at 24 Hours Post-dose
phospho-FLT3 (pFLT3) in blood assessed by Western blot at 24 hours post-dose
Measured: Cycle 1 Day 1, 24 hours post-dose.
Number of Participants With Suppression of pAKT at 4 Hours Post-dose
phospho-AKT (pAKT) in blood assessed by Western blot at 4 hours post-dose
Measured: Cycle 1 Day 1, 4 hours post-dose.
Number of Participants With Suppression of pAKT at 24 Hours Post-dose
phospho-AKT (pAKT) in blood assessed by Western blot at 24 hours post-dose
Measured: Cycle 1 Day 1, 24 hours post-dose.
Number of Participants With Suppression of pERK by PIA at 4 Hours Post-dose
Blood assay: Plasma inhibitory assay (PIA) measuring pERK in blood at 4 hours post-dose
Measured: Cycle 1 Day 1, 4 hours post-dose.
Number of Participants With Suppression of in pERK by PIA 24 Hours Post-dose
Blood assay: Plasma inhibitory assay (PIA) measuring pERK in blood at 24 hours post-dose
Measured: Cycle 1 Day 1, 24 hours post-dose.
Number of Participants With Suppression of pFLT3 by PIA at 4 Hours Post-dose
Blood assay: Plasma inhibitory assay (PIA) measuring pFLT3 in blood at 4 hours post-dose
Measured: Cycle 1 Day 1, 4 hours post-dose.
Number of Participants With Suppression of pFLT3 by PIA at 24 Hours Post-dose
Blood assay: Plasma inhibitory assay (PIA) measuring pFLT3 in blood at 24 hours post-dose
Measured: Cycle 1 Day 1, 24 hours post-dose.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2015 (estimated)
- Study start10 Apr 2015
- Primary completion8 Jun 2017
- Study completion8 Jun 2017
Why it stopped: Insufficient efficacy in Phase 1 dose-escalation portion of study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for AMLStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Spirita Oncology, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gautam Borthakur, MD, Study chair, MD Anderson Cancer Center Houston, TX 77030
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02418000
- Sponsor's protocol ID
- BSC-101-01
- Status last verified
- Mar 2019
- First submitted
- 18 Feb 2015
- Last updated
- 20 Mar 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02418000
- Acronym / sponsor ID
- BSC-101-01
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Insufficient efficacy in Phase 1 dose-escalation portion of study
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Spirita Oncology, LLCIndustry (pharma, biotech, devices)
- Study start
- 10 Apr 2015
- Primary completion
- 8 Jun 2017 (actual)
- Study completion
- 8 Jun 2017 (actual)
- First posted
- 16 Apr 2015 (estimated)
- Results
- Posted 5 Mar 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| E6201 240 mg/m^2 IV weekly | Experimental | Drug: E6201E6201 240 mg/m^2 administered IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) |
| E6201 320 mg/m^2 IV weekly | Experimental | Drug: E6201E6201 320 mg/m^2 administered IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) |
| E6201 160 mg/m^2 IV twice weekly | Experimental | Drug: E6201E6201 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) |
| E6201 240 mg/m^2 IV twice weekly | Experimental | Drug: E6201E6201 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) |
| E6201 320 mg/m^2 IV twice weekly | Experimental | Drug: E6201E6201 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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (10 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| E6201Also: Dual inhibitor of FLT3 and MEK1Single Group Assignment | Drug | E6201 160 mg/m^2 IV twice weekly, E6201 240 mg/m^2 IV twice weekly, E6201 240 mg/m^2 IV weekly, E6201 320 mg/m^2 IV twice weekly, E6201 320 mg/m^2 IV weekly |
Primary outcome
Maximum Tolerated Dose (MTD) of E6201
Time frame: 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.
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
Time frame: 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.
21 secondary outcomes
Overall Response Rate
Time frame: At the end of C1 and every 2 cycles thereafter through 6 months following last dose of study drug
Duration of Response
Time frame: At the end of C1 and every 2 cycles thereafter through 6 months following last dose of study drug
Progression-Free Survival
Time frame: From Cycle 1 Day 1 (C1D1) until death or study closure, up to 26 months
Overall Survival
Time frame: From C1D1 until death or study closure, up to 26 months
Pharmacokinetic Profile of E6201 in Plasma: Cmax
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.
Pharmacokinetics of E6201 in Plasma: Tmax
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.
Pharmacokinetic Profile of E6201 in Plasma: AUCT
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.
Pharmacokinetic Profile of E6201 in Plasma: AUCI
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.
Pharmacokinetic Profile of E6201 in Plasma: T1/2
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.
Pharmacokinetic Profile of E6201 in Plasma: CLobs
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.
Pharmacokinetic Profile of E6201 in Plasma: 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.
Number of Participants With Suppression of pERK at 4 Hours Post-dose
Time frame: Cycle 1 Day 1, 4 hours post-dose.
Number of Participants With Suppression of pERK at 24 Hours Post-dose
Time frame: Cycle 1 Day 1, 24 hours post-dose.
Number of Participants With Suppression of pFLT3 at 4 Hours Post-dose
Time frame: Cycle 1 Day 1, 4 hours post-dose.
Number of Participants With Suppression of pFLT3 at 24 Hours Post-dose
Time frame: Cycle 1 Day 1, 24 hours post-dose.
Number of Participants With Suppression of pAKT at 4 Hours Post-dose
Time frame: Cycle 1 Day 1, 4 hours post-dose.
Number of Participants With Suppression of pAKT at 24 Hours Post-dose
Time frame: Cycle 1 Day 1, 24 hours post-dose.
Number of Participants With Suppression of pERK by PIA at 4 Hours Post-dose
Time frame: Cycle 1 Day 1, 4 hours post-dose.
Number of Participants With Suppression of in pERK by PIA 24 Hours Post-dose
Time frame: Cycle 1 Day 1, 24 hours post-dose.
Number of Participants With Suppression of pFLT3 by PIA at 4 Hours Post-dose
Time frame: Cycle 1 Day 1, 4 hours post-dose.
Number of Participants With Suppression of pFLT3 by PIA at 24 Hours Post-dose
Time frame: Cycle 1 Day 1, 24 hours post-dose.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gautam Borthakur, MD study chair
MD Anderson Cancer Center Houston, TX 77030
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing E6201 in people with AML and MDS, run by Spirita Oncology, LLC at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Mar 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) of E6201 (time frame: Up to 6 weeks for each dose cohort). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2019.