Back to resultsAG-013736 (Axitinib) In Patients With Poor Prognosis Acute Myeloid Leukemia (AML) Or Myelodysplastic Syndrome (MDS)
Primary Purpose
Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
AG-013736 (Axitinib)
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia (AML)
Eligibility Criteria
Inclusion Criteria: Poor prognosis AML or MDS Histological confirmation of diagnosis White blood cell count less than or equal to 30,000/mm3 Adequate hepatic and renal function documented within 14 days prior to registration Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 No evidence of preexisting uncontrolled hypertension Not a suitable candidate for chemotherapy No prior systemic chemotherapy treatment for AML or MDS or treatment with an anti-angiogenesis agent Exclusion Criteria: Patients must not have exclusion criteria. Candidate for chemotherapy Patients with AML M3 (acute promyelocytic leukemia) Conditions that might confound the evaluation of safety or efficacy or increase patient risk.
Sites / Locations
- Pfizer Investigational Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Single arm study
Arm Description
Outcomes
Primary Outcome Measures
Percentage of Participants With Objective Response (OR)
Participants with OR based on a assessment of confirmed complete remission (CR) or partial remission (PR) according to Cheson criteria for Acute myeloid leukemia (AML) and Myelodysplastic syndrome (MDS). CR: those with > 20% cellularity of bone marrow biopsy, no presence of extramedullary leukemia for AML, <5 % myeloblast cells for bone marrow with peripheral blood value lasting at least 1 month and 2 months for AML and MDS respectively. PR : those with all criteria for CR except 5-25 % blasts in bone marrow and at least 50% decrease in blast over pretreatment for AML and MDS respectively.
Secondary Outcome Measures
Percentage of Participants With Hematologic Improvement (HI)
HI was described by the number of individual and positively affected cell lines (Erythroid response, Platelet response, Neutrophil response). Improvements must last at least 2 months.
Duration of Response (DR)
Time in days from the first documentation of objective tumor response to objective tumor progression or death due to any cause. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1). DR was calculated for the subgroup of participants with a confirmed objective tumor response.
Bone Marrow Micro Vessel Density (MVD)
Bone marrow MVD in tumors is a measure of angiogenesis and a prognostic indicator that correlates with an increased risk of metastasis in various cancers and with overall and relapse free survival in participants with AML or MDS. Bone marrow biopsies and bone marrow clot samples were assessed for MVD (cluster of differentiation 31 [CD31] staining).
Vascular Endothelial Growth Factor Receptor 1 (VEGFR-1) and VEFGR Receptor 2 (VEGFR-2) Phosphorylation
Vascular endothelial growth factor (VEGF) promotes cancer progression by inducing angiogenesis via VEGF receptors, signals directly through receptors VEGFR-1 and VEGFR-2. Change in biomarkers related to VEGFR signal transduction pathways after axitinib treatment was assessed. Mononuclear (MNC) cell VEGF receptor expression and phosphorylation was assessed by in situ western blot analysis. VEGFR-1 and VEGFR-2 evaluations were performed using samples from peripheral blood plasma, bone marrow aspirate, bone marrow (Core) biopsy and bone marrow clot.
Plasma Vascular Endothelial Growth Factor (VEGF) Concentration
VEGF promotes cancer progression by inducing angiogenesis via VEGF receptors, signals directly through receptors VEGFR-1 and VEGFR-2. Change in biomarkers related to VEGFR signal transduction pathways after axitinib treatment was assessed. Plasma VEGF concentration evaluations were performed using samples from peripheral blood plasma, bone marrow aspirate, bone marrow (Core) biopsy and bone marrow clot.
Population Pharmacokinetics of Axitinib (AG-013736)
Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.
Overall Survival (OS)
Time in days from the start of study treatment to date of death due to any cause. OS was calculated as (the death date minus the date of first dose of study medication plus 1). Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death). For participants who were alive, overall survival was censored at the last contact.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00071006
Brief Title
AG-013736 (Axitinib) In Patients With Poor Prognosis Acute Myeloid Leukemia (AML) Or Myelodysplastic Syndrome (MDS)
Official Title
Phase 2 Study Of AG-013736 In Patients With Poor Prognosis Acute Myeloid Leukemia (AML) Or Myelodysplastic Syndrome (MDS)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2012
Overall Recruitment Status
Completed
Study Start Date
September 2003 (undefined)
Primary Completion Date
July 2004 (Actual)
Study Completion Date
July 2004 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The study tests the safety and efficacy of axitinib in patients who have the hematologic disease of Acute Myeloid Leukemia or Myelodysplastic Syndrome. The study tests patients who have poor prognosis before entering the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Single arm study
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
AG-013736 (Axitinib)
Intervention Description
patients were treated with axitinib at starting dose of 5 mg BID continuous dosing.
Primary Outcome Measure Information:
Title
Percentage of Participants With Objective Response (OR)
Description
Participants with OR based on a assessment of confirmed complete remission (CR) or partial remission (PR) according to Cheson criteria for Acute myeloid leukemia (AML) and Myelodysplastic syndrome (MDS). CR: those with > 20% cellularity of bone marrow biopsy, no presence of extramedullary leukemia for AML, <5 % myeloblast cells for bone marrow with peripheral blood value lasting at least 1 month and 2 months for AML and MDS respectively. PR : those with all criteria for CR except 5-25 % blasts in bone marrow and at least 50% decrease in blast over pretreatment for AML and MDS respectively.
Time Frame
Baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 4 weeks up to 35 weeks
Secondary Outcome Measure Information:
Title
Percentage of Participants With Hematologic Improvement (HI)
Description
HI was described by the number of individual and positively affected cell lines (Erythroid response, Platelet response, Neutrophil response). Improvements must last at least 2 months.
Time Frame
Baseline, Week 2 thereafter every 4 weeks up to 35 weeks and follow up (at least 30 days after last dose)
Title
Duration of Response (DR)
Description
Time in days from the first documentation of objective tumor response to objective tumor progression or death due to any cause. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1). DR was calculated for the subgroup of participants with a confirmed objective tumor response.
Time Frame
First documentation of objective response until objective disease progression or discontinuation from the study due to any cause assessed every 4 weeks up to 35 weeks
Title
Bone Marrow Micro Vessel Density (MVD)
Description
Bone marrow MVD in tumors is a measure of angiogenesis and a prognostic indicator that correlates with an increased risk of metastasis in various cancers and with overall and relapse free survival in participants with AML or MDS. Bone marrow biopsies and bone marrow clot samples were assessed for MVD (cluster of differentiation 31 [CD31] staining).
Time Frame
Day 1, Week 2 thereafter every 4 weeks up to 35 weeks
Title
Vascular Endothelial Growth Factor Receptor 1 (VEGFR-1) and VEFGR Receptor 2 (VEGFR-2) Phosphorylation
Description
Vascular endothelial growth factor (VEGF) promotes cancer progression by inducing angiogenesis via VEGF receptors, signals directly through receptors VEGFR-1 and VEGFR-2. Change in biomarkers related to VEGFR signal transduction pathways after axitinib treatment was assessed. Mononuclear (MNC) cell VEGF receptor expression and phosphorylation was assessed by in situ western blot analysis. VEGFR-1 and VEGFR-2 evaluations were performed using samples from peripheral blood plasma, bone marrow aspirate, bone marrow (Core) biopsy and bone marrow clot.
Time Frame
Day 1, Week 2 thereafter every 4 weeks up to 35 weeks and follow up (at least 30 days after last dose)
Title
Plasma Vascular Endothelial Growth Factor (VEGF) Concentration
Description
VEGF promotes cancer progression by inducing angiogenesis via VEGF receptors, signals directly through receptors VEGFR-1 and VEGFR-2. Change in biomarkers related to VEGFR signal transduction pathways after axitinib treatment was assessed. Plasma VEGF concentration evaluations were performed using samples from peripheral blood plasma, bone marrow aspirate, bone marrow (Core) biopsy and bone marrow clot.
Time Frame
Day 1, Week 2 thereafter every 4 weeks up to 35 weeks and follow up (at least 30 days after last dose)
Title
Population Pharmacokinetics of Axitinib (AG-013736)
Description
Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.
Time Frame
Day 1 (pre-dose) and every 4 weeks up to 35 weeks
Title
Overall Survival (OS)
Description
Time in days from the start of study treatment to date of death due to any cause. OS was calculated as (the death date minus the date of first dose of study medication plus 1). Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death). For participants who were alive, overall survival was censored at the last contact.
Time Frame
Baseline to death due to any cause or at least every 3 months after discontinuation of study treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Poor prognosis AML or MDS
Histological confirmation of diagnosis
White blood cell count less than or equal to 30,000/mm3
Adequate hepatic and renal function documented within 14 days prior to registration
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
No evidence of preexisting uncontrolled hypertension
Not a suitable candidate for chemotherapy
No prior systemic chemotherapy treatment for AML or MDS or treatment with an anti-angiogenesis agent
Exclusion Criteria:
Patients must not have exclusion criteria.
Candidate for chemotherapy
Patients with AML M3 (acute promyelocytic leukemia)
Conditions that might confound the evaluation of safety or efficacy or increase patient risk.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Pfizer Investigational Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A4061013&StudyName=AG-013736%20%28Axitinib%29%20In%20Patients%20With%20Poor%20Prognosis%20Acute%20Myeloid%20Leukemia%20%28AML%29%20Or%20Myelodysplastic%20Syndrome%20%28MDS%29
Description
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Learn more about this trial
AG-013736 (Axitinib) In Patients With Poor Prognosis Acute Myeloid Leukemia (AML) Or Myelodysplastic Syndrome (MDS)
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