Aflibercept in Treating Patients With Myelodysplastic Syndromes

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00509249
Recruitment Status : Terminated (Early termination for discouraging results)
First Posted : July 31, 2007
Results First Posted : January 8, 2015
Last Update Posted : January 8, 2015
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This phase II trial is studying how well aflibercept works in treating patients with myelodysplastic syndromes. Aflibercept may be able to carry cancer-killing substances directly to myelodysplastic syndrome cells. It may also stop the growth of cancer cells by blocking blood flow to the cancer

Condition or disease Intervention/treatment Phase
Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative Chronic Myelomonocytic Leukemia de Novo Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable Previously Treated Myelodysplastic Syndromes Secondary Myelodysplastic Syndromes Biological: ziv-aflibercept Other: laboratory biomarker analysis Other: pharmacological study Phase 2

Detailed Description:


I. To determine the antitumor activity of aflibercept as assessed by the hematological response rate.

II. To determine overall and progression-free survival in patients with myelodysplastic syndromes.

III. To assess hematologic improvement and time to leukemic transformation. IV. To assess the toxicity profile of aflibercept in this patient population. V. To perform correlative studies to better understand the ability of aflibercept to reach and modulate its respective targets.

OUTLINE: This is a multicenter study.

Patients will receive aflibercept IV over 1 hour on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Blood and bone marrow samples will be obtained periodically for pharmacokinetic and biomarker correlative studies. Pharmacokinetic analysis by ELISA; anti-aflibercept antibody measurements; analysis of VEGF and VEGFR expression; and analysis of gene expression by quantitative PCR will be conducted. The effect of aflibercept on apoptosis and proliferation of CD34+ cells will also be analyzed by flow cytometry based assays.

After completion of study treatment, patients are followed periodically.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of VEGF Trap (NSC 724770) in Patients With MDS
Study Start Date : September 2007
Actual Primary Completion Date : December 2010
Actual Study Completion Date : December 2010

Arm Intervention/treatment
Experimental: Arm I
Patients will receive aflibercept IV at 4 mg/kg over 1 hour on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Biological: ziv-aflibercept
Given IV
Other Names:
  • aflibercept
  • vascular endothelial growth factor trap
  • VEGF Trap
  • Zaltrap

Other: laboratory biomarker analysis
Correlative studies

Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Primary Outcome Measures :
  1. Hematological Response Rate [ Time Frame: Up to 3 years ]
    Complete Response (CR): repeat bone marrow (BM) shows <5% myeloblasts, and peripheral blood values lasting ≥ 2 months of hemoglobin (hgb) (>110 g/L), neutrophils (≥1.0x10^9/L), platelets (≥100x10^9/L), blasts (0%) and no dysplasia. Partial Response (PR): same as CR for peripheral blood except BM shows blasts decrease by ≥ 50% but still > 5% or a less advanced FAB classification from pretreatment. Hematological response=CR+PR.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed myelodysplastic syndromes (MDS), including any of the following:

    • Secondary MDS
    • MDS/myeloproliferative disorders (MPD) (e.g., chronic myelomonocytic leukemia or atypical chronic myeloid leukemia)
    • IPSS scores of 0.5 or greater (≥ INT-1) OR transfusion dependent despite use of growth factors
    • No more than 20% blasts in the marrow
    • Patients who have not responded after 3 courses of hypomethylating agents (azacitidine or decitabine) OR; who are unable to tolerate hypomethylating agents OR who refused to receive hypomethylating agents are eligible for this study
  • ECOG performance status ≤ 2 (Karnofsky ≥ 60%)
  • Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
  • AST/ALT ≤ 2.5 x ULN
  • Creatinine ≤ 1.5 x ULN OR creatinine clearance ≥ 60 mL/min
  • Urine protein:creatinine ratio < 1 OR urine protein < 500 mg by 24-hour urine collection
  • PT INR ≤ 1.5
  • Patients with PT INR > 1.5 on full-dose anticoagulants (e.g., warfarin) are eligible provided both of the following criteria are met:

    • Patient has an in-range INR (usually between 2 and 3) and is on a stable dose of oral anticoagulant or low molecular weight heparin
    • Patient has no active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
  • Not pregnant or nursing
  • Fertile patients must use effective contraception during and for at least 6 months after completion of study treatment
  • Prior DNA-demethylating agent therapy or lenalidomide therapy allowed
  • Prior treatment with other molecular agents, such as thalidomide, valproic acid, or imatinib mesylate allowed

Exclusion Criteria:

  • Evidence of active malignancies other than squamous cell or basal cell carcinoma of the skin
  • Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in the study
  • Serious or non-healing wound, ulcer, or bone fracture
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
  • Significant traumatic injury within the past 28 days
  • Clinically significant cardiovascular disease, including any of the following:

    • History of cerebrovascular accident (CVA) within the past 6 months
    • Uncontrolled hypertension, defined as blood pressure > 150/100 mm Hg or systolic BP > 180 mm Hg if diastolic blood pressure < 90 mm Hg (on at least 2 repeated determinations on separate days) within the past 3 months
    • Myocardial infarction or unstable angina within the past 6 months
    • New York Heart Association class III or IV congestive heart failure, serious cardiac arrhythmia requiring medication, or unstable angina pectoris within the past 6 months
  • Clinically significant peripheral vascular disease within the past 6 months
  • Pulmonary embolism, deep vein thrombosis (DVT), or other thromboembolic event within the past 6 months
  • Evidence of bleeding diathesis or coagulopathy
  • Concurrent uncontrolled illness including, but not limited to, ongoing or active infection or psychiatric illness/social situation that would limit compliance with study requirements
  • Prior cytotoxic chemotherapy for MDS
  • Molecular therapy or immunosuppressive agents (including steroids) within the past 3 weeks
  • Other prior antiangiogenesis agents
  • Coronary artery bypass graft (CABG) within the past 6 months
  • Valproic acid should be discontinued at least 24 hours before aflibercept administration, unless needed for seizure control
  • Major surgical procedure or open biopsy within the past 28 days
  • Core biopsy (other than bone marrow biopsy) within the past 7 days
  • Anticipation of need for major surgical procedures during the course of the study
  • Patients may not be receiving any other investigational agents

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00509249

United States, California
City of Hope Medical Center
Duarte, California, United States, 91010
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Mark Kirschbaum City of Hope Medical Center

Responsible Party: National Cancer Institute (NCI) Identifier: NCT00509249     History of Changes
Other Study ID Numbers: NCI-2009-00180
N01CM62209 ( U.S. NIH Grant/Contract )
CDR0000558101 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted: July 31, 2007    Key Record Dates
Results First Posted: January 8, 2015
Last Update Posted: January 8, 2015
Last Verified: November 2012

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
Pathologic Processes
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Leukemia, Myeloid
Endothelial Growth Factors
Growth Substances
Physiological Effects of Drugs