Cediranib Maleate in Treating Patients With Relapsed, Refractory, or Untreated Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

Inclusion Criteria

• Histologically or cytologically confirmed acute myeloid leukemia (AML) ormyelodysplastic syndromes meeting 1 of the following criteria:
• Relapsed AML meeting any of the following criteria:
• Good-risk cytogenetics (inv[16], t[8;21], or t[15;17]) in second orgreater relapse
• Patients with AML t(15;17) must have failed prior tretinoin and arsenic-containing regimens AND progressed orrelapsed within 12 months of therapy
• In first or greater relapse
• Resistant AML
• Unable to achieve first complete remission after at least 2 inductionregimens
• Untreated AML meeting any of the following criteria:
• At least 60 years of age
• Preceding MDS
• MDS
• International Prognosis Scoring System (IPSS) risk groupof intermediate-2 or higher
• Patients with relapsed disease after allogeneic hematopoietic stem cell transplantation (HSCT) must be off allimmunosuppressive medications for at least 30 days and have no symptoms orsigns of graft-vs-host disease
• No active CNS metastasis
• Patients with clinical signs of CNS disease or a history of CNS diseasewithin the past 6 months are required to undergo lumbar puncture to excludeCNS involvement
• No symptomatic leukostasis or requirement for leukapheresis
• Not eligible for allogeneic HSCTAND no suitable donor at the time of study entry
• Patients who areeligible for HSCT, informed of the option, and choose not to proceed to HSCTare allowed
• ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
• Bilirubin normal
• AST and/or ALT ≤ 2.5 times upper limit of normal
• Creatinine normal OR creatinine clearance ≥ 60 mL/min
• No proteinuria ≥ 1+ on 2 consecutive urinalysis taken ≥ 1 week apart
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No HIV positivity
• LVEF ≥ 45% by echocardiography
• Mean QTc ≤ 500 msec (with Bazett's correction)
• No other significant ECG abnormality
• No history of familial long QT syndrome
• No disseminated intravascular coagulation
• No history of allergic reactions attributed to compounds of similar chemical orbiological composition to AZD2171
• No concurrent uncontrolled illness, including, but not limited to, any of the following:
• Hypertension
• Thyroid disease
• Ongoing or active infection
• Symptomatic congestive heartfailure
• Unstable angina pectoris
• Cardiac arrhythmia
• NYHA class III-IV heart disease
• NYHA class II heart disease controlled with treatment allowed
• Psychiatric illness or social situations that would limit study compliance
• See Disease Characteristics
• More than 4 weeks since prior chemotherapy (6 weeks fornitrosoureas or mitomycin C), radiotherapy, or major surgery and recovered
• Hydroxyurea allowed to control peripheral blast count> 20,000/mcL prior to study entry and during the first 3 days of study therapy
• More than 4 weeks since prior and no concurrent growth factor or other cytokine support
• At least 30 days since prior investigational agents or participation in aninvestigational trial
• No more than 3 prior courses of induction chemotherapy
• Induction chemotherapyis defined as that intended to induce complete remission and given at a time thatthe patient has active disease
• No concurrent CYP interactive medications
• No other concurrent investigational agents
• No concurrent drugs or biologics with proarrhythmic potential
• Prior and concurrent hydroxyurea allowed to control peripheral blast count> 20,000/mcL during the first 3 days of study therapy