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

Phase 2

Completed

Conditions: Acute Myeloid Leukemia (AML)
Myelodysplastic Syndrome

Interventions: Drug: AG-013736 (Axitinib)

Registration Number: NCT00071006

Lead Sponsor: Pfizer

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 12

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Single arm study	AG-013736 (Axitinib)	-

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Objective Response (OR)	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	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

Name	Time	Method
Percentage of Participants With Hematologic Improvement (HI)	Baseline, Week 2 thereafter every 4 weeks up to 35 weeks and follow up (at least 30 days after last dose)	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)	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	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)	Day 1, Week 2 thereafter every 4 weeks up to 35 weeks	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	Day 1, Week 2 thereafter every 4 weeks up to 35 weeks and follow up (at least 30 days after last dose)	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	Day 1, Week 2 thereafter every 4 weeks up to 35 weeks and follow up (at least 30 days after last dose)	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)	Day 1 (pre-dose) and every 4 weeks up to 35 weeks	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)	Baseline to death due to any cause or at least every 3 months after discontinuation of study treatment	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.