Brief Title
Cediranib Maleate in Treating Patients With Relapsed, Refractory, or Untreated Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
Official Title
A Phase II Study of AZD2171 in the Treatment of Patients With Acute Leukemia and Myelodysplastic Syndrome.
Brief 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.
Detailed Description
PRIMARY OBJECTIVES:
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).
SECONDARY OBJECTIVES:
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 techniques.
After completion of study treatment, patients are followed up at 3 months and then every 6
months for up to 2 years.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
The Number of Confirmed Disease Response: Complete Response (CR), Partial Response (PR), and Hematologic Improvement (HI). A Confirmed Response is Defined to be an Objective Status of CR, PR, or HI Noted on 2 Consecutive Evaluations.
Secondary Outcome
Overall Survival
Condition
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Intervention
cediranib maleate
Study Arms / Comparison Groups
Treatment (enzyme inhibitor therapy)
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
39
Start Date
May 2008
Completion Date
March 2012
Primary Completion Date
July 2011
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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Mark Juckett, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00475150
Organization ID
NCI-2009-00129
Secondary IDs
NCI-2009-00129
Responsible Party
Sponsor
Study Sponsor
National Cancer Institute (NCI)
Study Sponsor
Mark Juckett, Principal Investigator, Mayo Clinic
Verification Date
December 2016