Selumetinib in Treating Patients With Recurrent or Refractory Acute Myeloid Leukemia
Condition: Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Promyelocytic Leukemia (M3); Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Promyelocytic, Acute; Myelodysplastic Syndromes; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases
Intervention: selumetinib
Intervention description: Given PO
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 47.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II clinical trial is studying how well selumetinib works in treating patients with
      recurrent or refractory acute myeloid leukemia. Selumetinib may stop the growth of cancer by
      blocking some of the enzymes needed for cell growth
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed diagnosis of 1 of the following:

               -  Relapsed or refractory acute myeloid leukemia (AML)

               -  Secondary AML including AML arising from antecedent hematologic diseases (e.g.,
                  myelodysplastic syndrome, myeloproliferative disorders, or therapy-related AML)

          -  Elderly patients ≥ 60 years of age, previously untreated, and who are not candidates
             for or have refused standard chemotherapy are eligible for this trial

          -  Patients with relapsed acute promyelocytic leukemia (APL) who are FLT3+ and have
             failed both tretinoin and arsenic therapy are eligible for this trial

          -  No known active CNS disease

          -  ECOG performance status (PS) 0-2 or Karnofsky PS 60-100%

          -  Total bilirubin ≤ 2 mg/dL (unless due to disease, hemolysis, or Gilbert disease)

               -  In patients with associated hemolysis or Gilbert disease, a bilirubin of > 2
                  mg/dL is allowed as a result of predominantly unconjugated hyperbilirubinemia

          -  AST/ALT < 3 times upper limit of normal

          -  Creatinine < 2 mg/dL

          -  Baseline pulse oximetry > 92%

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception prior to, during, and for 4 weeks
             (16 week for males) after completion of study treatment

          -  Recovered from prior therapy

          -  At least 2 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) or
             radiotherapy

               -  Hydroxyurea may be administered for the first 7 days of therapy in patients with
                  rapidly rising white count (WBC > 20 K/μL)

          -  At least 4 weeks since prior investigational agents

          -  No prior MEK inhibitors

          -  No concurrent medication that can prolong the QT interval

          -  No other concurrent investigational agents

          -  No concurrent combination antiretroviral therapy for HIV-positive patients

        Exclusion Criteria:

          -  History of allergic reactions attributed to compounds of similar chemical or
             biological composition to AZD6244 or its excipient Captisol®

          -  QTc interval > 450 msecs or other factors that increase the risk of QT prolongation or
             arrhythmic events (e.g., heart failure, hypokalemia, or family history of long QT
             interval syndrome), including New York Heart Association class III or IV heart failure

          -  Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g., inflammatory
             bowel disease), or significant bowel resection that would preclude adequate absorption

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection or psychiatric illness or social situations that would limit compliance with
             study requirements