Know Cancer

forgot password

A Phase II Study of AZD2171 in the Treatment of Patients With Acute Leukemia and Myelodysplastic Syndrome

Phase 2
18 Years
Open (Enrolling)
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

Thank you

Trial Information

A Phase II Study of AZD2171 in the Treatment of Patients With Acute Leukemia and Myelodysplastic Syndrome


I. Evaluate the objective response rate in patients with relapsed, refractory, or untreated
acute myeloid leukemia or high-risk myelodysplastic syndromes treated with AZD2171
(cediranib maleate).


I. Determine the toxicity of this drug in these patients. II. Determine the response
duration, event-free survival, and overall survival of patients treated with this drug.

III. Determine the hematological response rate in patients treated with this drug.

OUTLINE: This is a multicenter study. Patients are stratified according to disease (acute
myeloid leukemia vs myelodysplastic syndromes).

Patients receive oral cediranib maleate once daily (QD) on days 1-28. Treatment repeats
every 28 days for up to 26 courses in the absence of disease progression or unacceptable
toxicity. Patients undergo bone marrow biopsy at baseline and on day 28 for correlative
studies. Samples are analyzed for circulating endothelial cells, VEGF receptor expression,
and leukemic blasts via flow cytometry and microvessel density via histopathological

After completion of study treatment, patients are followed up at 3 months and then every 6
months for up to 2 years.

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

- 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

- Untreated AML meeting any of the following criteria:

- At least 60 years of age

- Preceding 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

- 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

- 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

- 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

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Confirmed disease response

Outcome Description:

Defined to be an objective status of CR, PR or HI noted on 2 consecutive evaluations.

Outcome Time Frame:

At the end of courses 1 and 3 and every 3 courses thereafter

Safety Issue:


Principal Investigator

Mark Juckett

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mayo Clinic


United States: Food and Drug Administration

Study ID:




Start Date:

May 2008

Completion Date:

Related Keywords:

  • 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
  • Congenital Abnormalities
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Myelodysplastic Syndromes
  • Preleukemia



Howard University Hospital Washington, District of Columbia  20060
Johns Hopkins University Baltimore, Maryland  21205
University of Wisconsin Hospital and Clinics Madison, Wisconsin  53792-0001
Mayo Clinic in Florida Jacksonville, Florida  32224
Wayne State University Detroit, Michigan  48202