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

May 31, 2012 updated by: Pfizer

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • Pfizer Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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: Single arm study
Drug: AG-013736 (Axitinib)
patients were treated with axitinib at starting dose of 5 mg BID continuous dosing.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Objective Response (OR)
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
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)
Time Frame: 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.
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 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
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)
Time Frame: 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).
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
Time Frame: 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.
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
Time Frame: 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.
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)
Time Frame: 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.
Day 1 (pre-dose) and every 4 weeks up to 35 weeks
Overall Survival (OS)
Time Frame: 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.
Baseline to death due to any cause or at least every 3 months after discontinuation of study treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Pfizer

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2003

Primary Completion (Actual)

July 1, 2004

Study Completion (Actual)

July 1, 2004

Study Registration Dates

First Submitted

October 9, 2003

First Submitted That Met QC Criteria

October 10, 2003

First Posted (Estimate)

October 13, 2003

Study Record Updates

Last Update Posted (Estimate)

June 8, 2012

Last Update Submitted That Met QC Criteria

May 31, 2012

Last Verified

May 1, 2012

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • A4061013

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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