Selumetinib and Azacitidine in High Risk Chronic Blood Cancers
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Chicago
About this trial
This is a phase I, open-label, dose-escalation study to determine the MTD of selumetinib when combined with the standard dose of azacitidine. Treatment will begin within 28 days of screening procedures. Treatment will continue indefinitely, provided that the patient continues to derive benefit. A patient will be taken off study for reasons described in detail in section 3.12 including disease progression, unacceptable toxicity, inter-current illness, withdrawal of consent, or at the discretion of the investigator. Patients will be followed for 12 weeks after the last dose of study drug, until any study treatment related toxicities have stabilized, or until death. The total duration of the study is expected to be approximately 24 months.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age greater than or equal to 18 years of age
No history of prior exposure to a MEK inhibitor
ECOG performance status of ≤ 2
Adequate renal function, defined as serum creatinine ≤ 1.5 x ULN or creatinine clearance >30 mL/min based on the Cockroft-Gault equation: (140 - Age) x (weight in kg) x (0.85 if female) / 72 x serum creatinine
Disqualifiers
Receipt of any anti-cancer therapy within 14 days prior to study entry, with the exception of hydroxyurea. If clinically indicated in order to keep WBC <30,000/uL, hydroxyurea may be continued through the first cycle.
Concurrent active malignancy, with the exception of early stage basal cell or squamous cell skin cancer
Uncontrolled hypertension (BP >150/95 mmHg despite medical therapy)
Acute coronary syndrome within 6 months prior to starting treatment
Trial design
Design model
Single group
Treatments tested in this trial
Azacitidine
DrugPatients will receive azacitidine 75 mg/m2 as a subcutaneous injection on days 1-7. The dose of azacitidine 75 mg/m2 will remain unchanged, unless a dose reduction is required based on toxicities (dose level -1 = selumetinib 50 mg PO twice daily and azacitidine 50 mg/m2). Subjects will continue on this schedule in cycles of 28 days duration in the absence of disease progression
Selumetinib
DrugPatients will receive selumetinib administered by mouth on days 8-21. The starting dose cohort (dose level 1) will receive selumetinib 50 mg PO twice daily on days 8-21. Subsequent planned doses include selumetinib 75 mg PO twice daily (dose level 2) and selumetinib 100 mg PO twice daily (dose level 3). Subsequent dose levels will only be given once the prior dose level has shown acceptable safety. Subjects will continue on this schedule in cycles of 28 days duration in the absence of disease progression.
Treatment groups
18 Participants
are divided into 1 treatment groupGroup A: Azacitidine and selumetinibExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Number of patients with adverse events
To determine the maximum tolerated dose (MTD) of selumetinib when combined with azacitidine and measure any toxicities that may arise.
Time frame
Up to 24 months.Secondary outcomes
1
Time to completion of next generation sequencing panel.
To assess the feasibility of prospectively screening patients for RAS pathway activating mutations by next generation sequencing at our center in the context of a clinical trial.
Time frame
From the start of treatment to the record of patient death from any cause, or 100 months, whichever comes first.2
Rate of overall response.
Calculated by complete response + partial response + hematologic improvement.
Time frame
From the start of treatment to the first record of response, up to 100 months, whichever comes first.3
Rate of symptom response.
Time frame
From the start of treatment to the first record of symptom response, up to 100 months, whichever comes first.4
Rate of overall survival.
Time frame
From the start of treatment to the date of death, not to exceed 100 months, whichever comes first.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov