- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00475150
Cediranib Maleate in Treating Patients With Relapsed, Refractory, or Untreated Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
A Phase II Study of AZD2171 in the Treatment of Patients With Acute Leukemia and Myelodysplastic Syndrome.
Study Overview
Status
Conditions
- Recurrent Adult Acute Myeloid Leukemia
- Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
- Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
- Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
- Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
- Secondary Acute Myeloid Leukemia
- Untreated Adult Acute Myeloid Leukemia
- Previously Treated Myelodysplastic Syndromes
- Secondary Myelodysplastic Syndromes
- Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
- de Novo Myelodysplastic Syndromes
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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District of Columbia
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Washington, District of Columbia, United States, 20060
- Howard University Hospital
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Florida
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Jacksonville, Florida, United States, 32224-9980
- Mayo Clinic in Florida
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Maryland
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Baltimore, Maryland, United States, 21287
- Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center
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Michigan
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Detroit, Michigan, United States, 48201
- Wayne State University/Karmanos Cancer Institute
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Wisconsin
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Madison, Wisconsin, United States, 53792
- University of Wisconsin Hospital and Clinics
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
|
Correlative studies
Given orally
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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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:
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At the end of cycles 1 and 3 and every 3 cycles thereafter up to 26 cycles
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival
Time Frame: Every cycle during treatment and every 6 months for up to 2 years after completion of study treatment
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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.
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Every cycle during treatment and every 6 months for up to 2 years after completion of study treatment
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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
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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:
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Every 3 courses during treatment and then at 3 months and every 6 months for up to 2 years after completion of study treatment
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Duration of Response
Time Frame: Every 3 courses up to 26 courses
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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.
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Every 3 courses up to 26 courses
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The Number of Patients That Report Adverse Events Possibly, Probably, or Definitely Related to AZD2171.
Time Frame: Continuously during treatment up to 26 courses
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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.
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Continuously during treatment up to 26 courses
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Mark Juckett, Mayo Clinic
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Disease
- Bone Marrow Diseases
- Hematologic Diseases
- Neoplastic Processes
- Precancerous Conditions
- Syndrome
- Myelodysplastic Syndromes
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Neoplasm Metastasis
- Preleukemia
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Cediranib
Other Study ID Numbers
- NCI-2009-00129 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- P30CA015083 (U.S. NIH Grant/Contract)
- N01CM62205 (U.S. NIH Grant/Contract)
- CDR0000544833
- MCCRC-MC048H
- MC048H (Other Identifier: Mayo Clinic)
- 7135 (Other Identifier: CTEP)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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