Cediranib Maleate in Treating Patients With Relapsed, Refractory, or Untreated Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
About this trial
This is an interventional treatment trial for Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Eligibility Criteria
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
Sites / Locations
- Howard University Hospital
- Mayo Clinic in Florida
- Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center
- Wayne State University/Karmanos Cancer Institute
- University of Wisconsin Hospital and Clinics
Arms of the Study
Arm 1
Experimental
Treatment (enzyme inhibitor therapy)
Patients receive oral cediranib maleate QD on days 1-28. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.