MEK Inhibitor MEK162, Idarubicin, and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

Not Recruiting

Trial ID: NCT02049801


This phase I trial studies the MEK inhibitor MEK162 to see if it is safe in patients when combined with idarubicin and cytarabine. MEK inhibitor MEK162 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as idarubicin and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving MEK inhibitor MEK162, cytarabine, and idarubicin may be an effective treatment for acute myeloid leukemia.

Official Title

A Phase I Study of MEK Inhibitor MEK162 Combined With Idarubicin and Cytarabine Induction in Patients With Relapsed/Refractory RAS-Mutated Acute Myeloid Leukemia

Stanford Investigator(s)

Steven Sanislo, MD
Steven Sanislo, MD

Clinical Professor, Ophthalmology


Inclusion Criteria:

   - Prior morphological diagnosis of AML other than acute promyelocytic leukemia according
   to the 2001 World Health Organization (WHO) diagnostic criteria; patients with
   biphenotypic, RAS-mutated acute leukemia are also eligible

   - Requiring salvage chemotherapy for persistent/refractory or relapsed disease after at
   least one course of conventional chemotherapy, e.g. with "7+3", as defined by
   persistence of >= 20% myeloid blasts on bone marrow aspirate or peripheral blood
   smear; a bone marrow biopsy is not routinely required, but should be obtained if the
   aspirate is dilute, hypocellular, or inaspirable; outside bone marrow examinations
   performed within the stipulated time period are acceptable for screening as long as
   the slides are reviewed at the study institution; flow cytometric analysis of the bone
   marrow aspirate should be performed according to institutional practice guidelines

   - Confirmed RAS mutation (NRAS or KRAS) or confirmed PTPN11 mutation, measured on
   peripheral blood or bone marrow aspirate as part of screening prior to study
   enrollment; mutation status must be confirmed within 45 days of initiation of therapy

   - Eastern Cooperative Oncology Group (ECOG) performance status =< 1

   - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 times upper
   limit of normal (ULN)

   - Serum bilirubin =< 2 times ULN

   - Serum creatinine =< 1.5 mg/dl and/or creatinine clearance >= 50 mL/min

   - Ejection fraction >= 50% by echocardiogram

   - Corrected QT (QTc) interval =< 480 ms

   - Ability to take oral medications

   - Ability to understand and the willingness to sign a written informed consent document

   - Ability to undergo standard induction chemotherapy

   - Ability to adhere to the study visit schedule and other protocol requirements

   - Life expectancy of greater than 2 months

   - Negative serum beta-human chorionic gonadotropin (HCG) test (female patient of
   childbearing potential only) performed locally within 72 hrs prior to first dose

Exclusion Criteria:

   - Concomitant treatment with other anti-neoplastic agents, with the exception of

   - Anti-neoplastic treatment less than 14 days prior to enrollment, with the exceptions
   of hydroxyurea or, in the case of a patient with primary refractory AML, prior
   induction chemotherapy

   - Prior therapy with a MEK inhibitor

   - Uncontrolled opportunistic infection or treatment for opportunistic infection within 4
   weeks of first day of study drug dosing

   - Other medical or psychiatric illness or organ dysfunction or laboratory abnormality
   which in the opinion of the investigator would compromise the patient's safety or
   interfere with data interpretation, e.g., infection/inflammation, intestinal
   obstruction, unable to swallow medication, social/ psychological issues, etc.

   - History of allergic reactions attributed to compounds of similar chemical or biologic
   composition to MEK162, anthracycline, or cytarabine

   - Known impairment of gastrointestinal (GI) function or GI disease that may
   significantly alter the absorption of MEK162 (e.g., ulcerative disease, uncontrolled
   nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection)

   - Previous or concurrent malignancy with the following exceptions:

      - Carcinoma in situ

      - Adequately treated skin basal cell or squamous cell carcinoma (adequate wound
      healing is required prior to study entry)

      - In situ carcinoma of the cervix, treated curatively and without evidence of
      recurrence for at least 3 years prior to the study

      - A primary malignancy which has been completely resected and in complete remission
      for >= 5 years

   - Impaired cardiovascular function or clinically significant cardiovascular diseases,
   including any of the following:

      - History of acute coronary syndromes (including myocardial infarction, unstable
      angina, coronary artery bypass grafting [CABG], coronary angioplasty, or
      stenting) < 6 months prior to screening

      - Symptomatic chronic heart failure

      - Evidence of clinically significant cardiac arrhythmias and/or conduction
      abnormalities < 6 months prior to screening except atrial fibrillation and
      paroxysmal supraventricular tachycardia

   - Uncontrolled arterial hypertension despite appropriate medical therapy

   - Patients who have neuromuscular disorders that are associated with elevated creatine
   kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral
   sclerosis, spinal muscular atrophy)

   - Known confirmed diagnosis of human immunodeficiency virus (HIV) infection or active
   viral hepatitis (hepatitis B or hepatitis C)

   - Any surgical procedure, excluding central venous catheter placement, bone marrow
   biopsy, lumbar puncture, or other minor procedures (e.g., skin biopsy) within 14 days
   of day 1; patients who have undergone major surgery =< 21 days prior to starting study
   drug or who have not recovered from side effects of such procedure are ineligible for
   the study

   - Pregnant or nursing (lactating) women confirmed by a positive hCG laboratory test

      - Women of child-bearing potential unless they are using highly effective methods
      of contraception throughout the study and for 30 days after study drug

   - Sexually active males unless they use a condom during intercourse while taking the
   drug and for 30 days after stopping treatment and should not father a child in this
   period; a condom is required to be used also by vasectomized men in order to prevent
   delivery of the drug via seminal fluid

   - Unwillingness or inability to comply with the protocol

   - Known active leukemia of the central nervous system

   - Known history of Gilbert's syndrome

   - History or current evidence of retinal pigment epithelial detachment (RPED), retinal
   vein occlusion (RVO), or predisposing factors to RPED or RVO (e.g. uncontrolled
   glaucoma or ocular hypertension, uncontrolled diabetes mellitus, hyperviscosity or
   hypercoagulability syndromes)

   - History of retinal degenerative disease


drug: MEK inhibitor MEK162

drug: idarubicin

drug: cytarabine

other: pharmacological study

other: laboratory biomarker analysis

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Jack C. Taw

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