Status:
RECRUITING
Selumetinib and Azacitidine in High Risk Chronic Blood Cancers
Lead Sponsor:
University of Chicago
Conditions:
Chronic Myeloid Leukemia
Myelofibroses
Eligibility:
All Genders
18+ years
Phase:
PHASE1
Brief 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 procedure...
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 strat...
Eligibility Criteria
Inclusion
- 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:
- a. 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).
- b. 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.
- c. 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
- 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
Exclusion
- 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
- 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
Key Trial Info
Start Date :
September 4 2018
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
September 4 2027
Estimated Enrollment :
18 Patients enrolled
Trial Details
Trial ID
NCT03326310
Start Date
September 4 2018
End Date
September 4 2027
Last Update
December 29 2025
Active Locations (1)
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1
The University of Chicago
Chicago, Illinois, United States, 60637