AG-013736 (Axitinib) In Patients With Poor Prognosis Acute Myeloid Leukemia (AML) Or Myelodysplastic Syndrome (MDS)

Study Overview
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Brief Summary
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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.

Official Title
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Phase 2 Study Of AG-013736 In Patients With Poor Prognosis Acute Myeloid Leukemia (AML) Or Myelodysplastic Syndrome (MDS)

Conditions
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Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome

Intervention / Treatment
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* Drug: AG-013736 (Axitinib)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single arm study<br> | Drug: AG-013736 (Axitinib)<br>* patients were treated with axitinib at starting dose of 5 mg BID continuous dosing.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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 Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline, Week 2 thereafter every 4 weeks up to 35 weeks and follow up (at least 30 days after last dose) | 
| 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. | 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 | 
| 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). | Day 1, Week 2 thereafter every 4 weeks up to 35 weeks | 
| 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. | Day 1, Week 2 thereafter every 4 weeks up to 35 weeks and follow up (at least 30 days after last dose) | 
| 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. | Day 1, Week 2 thereafter every 4 weeks up to 35 weeks and follow up (at least 30 days after last dose) | 
| 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. | Day 1 (pre-dose) and every 4 weeks up to 35 weeks | 
| 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. | Baseline to death due to any cause or at least every 3 months after discontinuation of study treatment |