Selumetinib and Azacitidine in High Risk Chronic Blood Cancers

Launched by UNIVERSITY OF CHICAGO · Oct 25, 2017

Keywords

ClinConnect Summary

This clinical trial is studying the combination of two medications, selumetinib and azacitidine, to see how well they work together in treating patients with high-risk chronic blood cancers, specifically chronic myeloid leukemia and myelofibrosis. The goal is to find the highest safe dose of selumetinib that can be used alongside the standard dose of azacitidine. If you’re an adult aged 18 or older with specific types of these blood cancers and have not previously been treated with a MEK inhibitor, you may be eligible to participate.

Participants in this trial can expect to begin treatment within 28 days after screening and continue as long as they are benefiting from the treatment. The study will last about 24 months, and you will be monitored for any side effects or changes in your condition. It’s important to know that you could leave the study for various reasons, such as if your disease worsens or if you experience unacceptable side effects. Throughout the study, you will have regular follow-ups to ensure your health and safety.

Gender

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Eligibility criteria

• Inclusion Criteria:
• 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 Criteria:
• 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:
• • 1. Uncontrolled hypertension (BP \>150/95 mmHg despite medical therapy)
• • 2. Acute coronary syndrome within 6 months prior to starting treatment
• • 3. Uncontrolled angina despite medical therapy
• • 4. Symptomatic heart failure (NYHA class II-IV despite medical therapy)
• • 5. Baseline LV EF \<50% measured by either echocardiography or MUGA scan
• • 6. Severe valvular heart disease
• • 7. Atrial fibrillation with ventricular rate \>100 bpm on EKG at rest.
• * Ophthalmologic conditions, including any of the following:
• • 1. Current or past history of central serous retinopathy
• • 2. Current or past history of retinal vein occlusion
• • 3. 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