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

• Status: Terminated
• Trial end date: 2017-06-08
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Spirita Oncology, LLC; Strategia Therapeutics

Criteria

Inclusion Criteria:

• Males and females ≥ 18 years of age

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

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

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

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

• Adequate renal and hepatic function:

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

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

• ALT and AST ≤ 5 times ULN

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

• Ability to provide written informed consent

Exclusion Criteria:

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

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

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

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

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

• Active, uncontrolled infection

• Known hypersensitivity to any study drug component

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

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

• Pregnancy or lactation