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) 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||Drug: cediranib maleate Other: laboratory biomarker analysis||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase II Study of AZD2171 in the Treatment of Patients With Acute Leukemia and Myelodysplastic Syndrome.|
- 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. [ Time Frame: At the end of cycles 1 and 3 and every 3 cycles thereafter up to 26 cycles ]
Complete Response (CR) requires a repeat bone marrow with < 5% myeloblasts, hemoglobin ≥ 11 g/dl, neutrophils ≥ 1000/mm3, platelets ≥ 100,000/mm3, and no circulating blasts.
Partial Response (PR) requires a bone marrow blast reduction of 50% or more, hemoglobin ≥ 11 g/dl, neutrophils ≥ 1000/mm3, platelets ≥ 100,000/mm3, and no circulating blasts.
Hematologic Improvement (HI) requires one of the following:
- RBC transfusion independent participants are required to have >1.5 g/dL increase in hemoglobin,
- RBC transfusion-dependent participants are required to be transfusion independent,
- A 100% increase, and an absolute increase over 500mm^3 in Absolute Neutrophil Count,
- Participants with a pretreatment platelet count over 20,000/mm3 require an absolute increase of 30,000/mm^3 or more,
- Participants with platelet count below 20,000/mm3 require an increase over 20,000/mm^3 and by at least 100%.
- Overall Survival [ Time Frame: Every cycle during treatment and every 6 months for up to 2 years after completion of study treatment ]Defined as the time from date of registration to date of death due to any cause or date last known alive. The distribution of survival time will be estimated using the method of Kaplan-Meier.
- Progression-free Survival [ Time Frame: Every 3 courses during treatment and then at 3 months and every 6 months for up to 2 years after completion of study treatment ]
Defined as the time from date of registration to date that disease progression was documented, death, or last date that progression-free status was documented, whichever comes first. Estimated using the method of Kaplan-Meier.
Disease progression is defined as one of the following:
- A ≥ 50% increase in bone marrow blasts from the best response, or
- A 50% or greater decrement from maximum remission/response levels in neutrophils or platelets, or
- A reduction in hemoglobin concentration by at least 1.5 g/dl, or
- Transfusion dependence (without alternative explanation and sustained for at least 2 weeks).
- Duration of Response [ Time Frame: Every 3 courses up to 26 courses ]Measured from the time criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented. Estimated using the method of Kaplan-Meier.
- The Number of Patients That Report Adverse Events Possibly, Probably, or Definitely Related to AZD2171. [ Time Frame: Continuously during treatment up to 26 courses ]Graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. All adverse events determined to be possibly, probably, or definately related to AZD2171 are included in this analysis.
|Study Start Date:||May 2008|
|Study Completion Date:||March 2012|
|Primary Completion Date:||July 2011 (Final data collection date for primary outcome measure)|
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.
Drug: cediranib maleate
Other Names:Other: laboratory biomarker analysis
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 techniques.
After completion of study treatment, patients are followed up at 3 months and then every 6 months for up to 2 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00475150
|United States, District of Columbia|
|Howard University Hospital|
|Washington, District of Columbia, United States, 20060|
|United States, Florida|
|Mayo Clinic in Florida|
|Jacksonville, Florida, United States, 32224-9980|
|United States, Maryland|
|Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center|
|Baltimore, Maryland, United States, 21287|
|United States, Michigan|
|Wayne State University/Karmanos Cancer Institute|
|Detroit, Michigan, United States, 48201|
|United States, Wisconsin|
|University of Wisconsin Hospital and Clinics|
|Madison, Wisconsin, United States, 53792|
|Principal Investigator:||Mark Juckett||Mayo Clinic|