Cediranib Maleate in Treating Patients With Relapsed, Refractory, or Untreated Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
Condition: 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); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Neoplasm Metastasis; Myelodysplastic Syndromes; Syndrome
Intervention: cediranib maleate; laboratory biomarker analysis
Intervention description: Given orally; Correlative studies
Intervention MeSH terms: Cediranib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 39.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well cediranib maleate works in treating patients with
      relapsed, refractory, or untreated acute myeloid leukemia or high-risk myelodysplastic
      syndrome. Cediranib maleate may stop the growth of cancer cells by blocking some of the
      enzymes needed for cell growth and by blocking blood flow to the cancer.
    

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