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