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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00071006
First received: October 9, 2003
Last updated: May 31, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention Phase
Acute Myeloid Leukemia (AML)
Myelodysplastic Syndrome
Drug: AG-013736 (Axitinib)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 2 Study Of AG-013736 In Patients With Poor Prognosis Acute Myeloid Leukemia (AML) Or Myelodysplastic Syndrome (MDS)

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline, Week 2 thereafter every 4 weeks up to 35 weeks and follow up (at least 30 days after last dose) ] [ Designated as safety issue: No ]
    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 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 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Day 1, Week 2 thereafter every 4 weeks up to 35 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1, Week 2 thereafter every 4 weeks up to 35 weeks and follow up (at least 30 days after last dose) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1, Week 2 thereafter every 4 weeks up to 35 weeks and follow up (at least 30 days after last dose) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Day 1 (pre-dose) and every 4 weeks up to 35 weeks ] [ Designated as safety issue: No ]
    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 Frame: Baseline to death due to any cause or at least every 3 months after discontinuation of study treatment ] [ Designated as safety issue: No ]
    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.


Enrollment: 12
Study Start Date: September 2003
Study Completion Date: July 2004
Primary Completion Date: July 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single arm study Drug: AG-013736 (Axitinib)
patients were treated with axitinib at starting dose of 5 mg BID continuous dosing.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00071006

Locations
United States, Texas
Pfizer Investigational Site
Houston, Texas, United States, 77030
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00071006     History of Changes
Other Study ID Numbers: A4061013
Study First Received: October 9, 2003
Results First Received: February 25, 2012
Last Updated: May 31, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Axitinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014