Chronic Myeloid LeukemiaPhase 1NCT03326310
Selumetinib and Azacitidine in High Risk Chronic Blood Cancers
A Phase 1 study testing Azacitidine and Selumetinib in people with Chronic Myeloid Leukemia and Myelofibroses, run by University of Chicago at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Myeloid Leukemia, Myelofibroses
- What is being tested?
- Azacitidine and Selumetinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Sep 2018to 4 Sep 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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
- All of the following criteria must be met:
- Age greater than or equal to 18 years of age
- Histologic confirmation of one of the following:
- MDS fulfilling all the criteria below: i. International Prognostic Scoring System (IPSS) intermediate-2 or high risk MDS; or Revised International Prognostic Scoring System (IPSS-R) intermediate, high, or very high risk MDS ii. - relapsed/refractory disease iii. Requiring therapy based on the presence of one or more cytopenias (Hb <10 g/dL and/or red cell transfusion dependence, platelets- <50,000/μL, or ANC <1,000/ μL) or excess blasts (≥5% in the peripheral blood or bone marrow).
- MDS/MPN as defined by the WHO criteria, including CMML, atypical CML, and MDS/MPN-Unclassifiable fulfilling the criteria listed below i. relapsed/refractory disease ii. Requiring therapy based on the presence of one or more cytopenias (Hb <10 g/dL and/or red cell transfusion dependence, platelets <50,000/μL, or ANC <1,000/ μL), excess blasts (≥5% in the peripheral blood or bone marrow), or palpable splenomegaly iii. or previously untreated subsets (e.g atypical CML, MDS/MPN unclassifiable) requiring therapy as defined above and in whom no approved therapies exist.
- Myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis fulfilling the criteria listed below: i. Intermediate-2 or high risk disease according to the Dynamic International Prognostic Scoring System (DIPSS) classification ii. refractory or intolerant to JAK inhibitor therapy, or deemed - ineligible for ruxolitinib therapy due to pre- existing cytopenias (thrombocytopenia <50,000/uL, anemia hemoglobin <9g/dL or red cell transfusion dependence).Requiring further therapy based on the presence of one or more cytopenias (Hb <10 g/dL and/or red cell transfusion dependence, platelets <50,000/μL, or ANC <1,000/μL), excess blasts (≥5% in the peripheral blood or bone marrow), or palpable splenomegaly
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- 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
- Adequate liver function, defined as conjugated bilirubin ≤ 2 x ULN as well as aspartate transaminase (AST) and alanine aminotransaminase (ALT) ≤ 3 x ULN
- Patients must be at least 2 weeks from major surgery, radiation therapy, participation in other investigational trials and must have recovered from clinically significant toxicities of these prior treatments
- Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment
- Female and male patients must use an effective contraceptive method during the study and for at least 6 months thereafter
- Ability to understand and willingness to sign a written informed consent document
Who cannot join
- Patients are excluded if any one of the following is present:
- 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
- Active cardiac conditions, including any of the following:
- Uncontrolled hypertension (BP >150/95 mmHg despite medical therapy)
- Acute coronary syndrome within 6 months prior to starting treatment
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- Uncontrolled angina despite medical therapy
- Symptomatic heart failure (NYHA class II-IV despite medical therapy)
- Baseline LV EF <50% measured by either echocardiography or MUGA scan
- Severe valvular heart disease
- Atrial fibrillation with ventricular rate >100 bpm on EKG at rest.
- Ophthalmologic conditions, including any of the following:
- Current or past history of central serous retinopathy
- Current or past history of retinal vein occlusion
- Intraocular pressure (IOP) >21 mmHg or uncontrolled glaucoma
- Any uncontrolled concurrent illness that, in the judgment of the investigators or treating physician, may put the patient at undo risk including but not limited to active infection, symptomatic cardiac or pulmonary disease, ventricular arrhythmia, or psychiatric illness.
- Pregnant or lactating patients
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
The University of Chicago
Chicago, Illinois, 60637
Melissa Fridstein, 773-702-9885, mfridstein@medicine.bsd.uchicago.edu
About this study
Official title: Phase I Study of MEK Inhibitor Selumetinib in Combination With Azacitidine in Patients With Higher Risk Chronic Myeloid Neoplasia: MDS, MDS/MPNs, and Myelofibrosis
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.
Read the detailed description
This is a phase I, open-label, dose-escalation study to determine the MTD of selumetinib when combined with the standard dose of azacitidine. For the purposes of DLT assessment, subjects will be stratified into 2 cohorts- cohort A will include subjects with MDS and MDS/MPN; cohort B will include subjects with myelofibrosis. Dose escalation will proceed independently in each of these cohorts. Determination of MTD will thus also proceed independently within each cohort. Three dose levels of selumetinib are planned for evaluation. Dose escalation will follow a 3+3 study design. Patients will be enrolled sequentially and stratified according to disease type as outlined above. An increased dose level will only open to accrual once at least 3 patients have been treated at the lower dose, followed for the defined DLT observation period (28 days, see section 2.8 below), and the lower dose level has been deemed safe.
The 3+3 dose escalation algorithm will proceed as follows:
- If 0/3 patients develop a DLT at a dose level, escalate to the next dose level.
- If 1/3 patients develops a DLT at a dose level, enroll 3 additional patients at that dose level.
- At that dose level, if 1/6 patients develops a DLT, escalate to the next dose level.
- If ≥2/6 patients develop a DLT, that dose level will be determined to be too toxic.
- If 2-3/3 patients develop a DLT at a dose level, that dose level will be determined to be too toxic.
- Six patients will be treated at the MTD.
- If the study progresses to dose level 3 with 0/3 patients experiencing a DLT, an additional 3 patients will be enrolled at that dose level to gain additional information regarding toxicity.
- If a dose level is determined to be too toxic and the next lower dose level only included 3 patients, an additional 3 patients will be treated at the lower dose level to confirm tolerability.
- If no patients have a DLT reported at dose level 3, that will be defined as the MTD and the dose will not be escalated above that level.
- Conditions
- Chronic Myeloid Leukemia, Myelofibroses
- Being tested
- Azacitidine, Selumetinib
- Keywords
- Chronic Myeloid Leukemia, Myelofibrosis, selumetinib, azacitidine
- Medical subject headings
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Primary Myelofibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzacitidineDrug
Also called Vidaza
Patients 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
SelumetinibDrug
Also called AZD6244
Patients 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.
| Study group | Role | What they receive |
|---|---|---|
| Azacitidine and selumetinib | Experimental | Subjects will receive azacitidine subcutaneously on days 1-7. Selumetinib will be administered on days 8-21. Subjects will continue on this schedule in cycles of 28 days duration in the absence of disease progression. Receives: Drug: Azacitidine; Drug: Selumetinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 24 months.
Secondary outcomes (5)
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.
Measured: From the start of treatment to the record of patient death from any cause, or 100 months, whichever comes first.
Rate of overall response.
Calculated by complete response + partial response + hematologic improvement.
Measured: From the start of treatment to the first record of response, up to 100 months, whichever comes first.
Rate of symptom response.
Measured: From the start of treatment to the first record of symptom response, up to 100 months, whichever comes first.
Rate of overall survival.
Measured: From the start of treatment to the date of death, not to exceed 100 months, whichever comes first.
Rate of progression free survival.
Measured: From the start of treatment to the first record of disease progression or the date of death, not to exceed 100 months, whichever comes first.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2017
- Study start4 Sep 2018
- Primary completion4 Sep 2027 (estimated)
- Study completion4 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by University of ChicagoThe sponsor's other registered studies.
- 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Chicago
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Olatoyosi Odenike, MD, Principal investigator, University of Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03326310
- Sponsor's protocol ID
- IRB17-0774
- Status last verified
- Dec 2025
- First submitted
- 13 Oct 2017
- Last updated
- 29 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of MEK Inhibitor Selumetinib in Combination With Azacitidine in Patients With Higher Risk Chronic Myeloid Neoplasia: MDS, MDS/MPNs, and Myelofibrosis
- ClinicalTrials.gov ID
- NCT03326310
- Acronym / sponsor ID
- IRB17-0774
- Conditions
- Chronic Myeloid Leukemia, Myelofibroses
- Keywords
- Chronic Myeloid Leukemia, Myelofibrosis, selumetinib, azacitidine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- University of ChicagoUniversity, hospital or other
- Study start
- 4 Sep 2018 (actual)
- Primary completion
- 4 Sep 2027 (estimated)
- Study completion
- 4 Sep 2027 (estimated)
- First posted
- 31 Oct 2017 (actual)
- Results
- Not posted in the source record
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 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.
Detailed description
This is a phase I, open-label, dose-escalation study to determine the MTD of selumetinib when combined with the standard dose of azacitidine. For the purposes of DLT assessment, subjects will be stratified into 2 cohorts- cohort A will include subjects with MDS and MDS/MPN; cohort B will include subjects with myelofibrosis. Dose escalation will proceed independently in each of these cohorts. Determination of MTD will thus also proceed independently within each cohort. Three dose levels of selumetinib are planned for evaluation. Dose escalation will follow a 3+3 study design. Patients will be enrolled sequentially and stratified according to disease type as outlined above. An increased dose level will only open to accrual once at least 3 patients have been treated at the lower dose, followed for the defined DLT observation period (28 days, see section 2.8 below), and the lower dose level has been deemed safe.
The 3+3 dose escalation algorithm will proceed as follows:
- If 0/3 patients develop a DLT at a dose level, escalate to the next dose level.
- If 1/3 patients develops a DLT at a dose level, enroll 3 additional patients at that dose level.
- At that dose level, if 1/6 patients develops a DLT, escalate to the next dose level.
- If ≥2/6 patients develop a DLT, that dose level will be determined to be too toxic.
- If 2-3/3 patients develop a DLT at a dose level, that dose level will be determined to be too toxic.
- Six patients will be treated at the MTD.
- If the study progresses to dose level 3 with 0/3 patients experiencing a DLT, an additional 3 patients will be enrolled at that dose level to gain additional information regarding toxicity.
- If a dose level is determined to be too toxic and the next lower dose level only included 3 patients, an additional 3 patients will be treated at the lower dose level to confirm tolerability.
- If no patients have a DLT reported at dose level 3, that will be defined as the MTD and the dose will not be escalated above that level.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Azacitidine and selumetinib | Experimental | Drug: Azacitidine, Drug: SelumetinibSubjects will receive azacitidine subcutaneously on days 1-7. Selumetinib will be administered on days 8-21. Subjects will continue on this schedule in cycles of 28 days duration in the absence of disease progression. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Age greater than or equal to 18 years of age
- Histologic confirmation of one of the following:
- 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
Key exclusion criteria (17 listed)
- 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
- Active cardiac conditions, including any of the following:
- Ophthalmologic conditions, including any of the following:
- Any uncontrolled concurrent illness that, in the judgment of the investigators or treating physician, may put the patient at undo risk including but not limited to active infection, symptomatic cardiac or pulmonary disease, ventricular arrhythmia, or psychiatric illness.
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 |
|---|---|---|
| AzacitidineAlso: VidazaPatients 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 | Drug | Azacitidine and selumetinib |
| SelumetinibAlso: AZD6244Patients 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. | Drug | Azacitidine and selumetinib |
Primary outcome
Number of patients with adverse events
Time frame: Up to 24 months.
To determine the maximum tolerated dose (MTD) of selumetinib when combined with azacitidine and measure any toxicities that may arise.
5 secondary outcomes
Time to completion of next generation sequencing panel.
Time frame: From the start of treatment to the record of patient death from any cause, or 100 months, whichever comes first.
Rate of overall response.
Time frame: From the start of treatment to the first record of response, up to 100 months, whichever comes first.
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.
Rate of overall survival.
Time frame: From the start of treatment to the date of death, not to exceed 100 months, whichever comes first.
Rate of progression free survival.
Time frame: From the start of treatment to the first record of disease progression or the date of death, not to exceed 100 months, whichever comes first.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Dec 2025.
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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.
Olatoyosi Odenike, MD principal investigator
University of Chicago
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Azacitidine and Selumetinib in people with Chronic Myeloid Leukemia and Myelofibroses, run by University of Chicago at 1 site 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 14 inclusion and 17 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: looking for participants now, as of the sponsor's last update on 29 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Cancer Clinical Trials Office (1-855-702-8222, cancerclinicaltrials@bsd.uchicago.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients with adverse events (time frame: Up to 24 months.). 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 29 Dec 2025.