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LeukemiaPhase 2NCT00601991

A Multi-Center Phase 2 Study of VEGF Trap as a Single Agent in Acute Myeloid Leukemia

A Phase 2 study testing VEGF Trap, Bone marrow biopsy and bone marrow aspiration in people with Leukemia, run by Vanderbilt-Ingram Cancer Center.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

RATIONALE: Aflibercept may stop the growth of cancer cells by blocking blood flow to the cancer. PURPOSE: This phase II trial is studying how well aflibercept works in treating patients with advanced refractory, relapsed, or untreated acute myeloid leukemia. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Leukemia
What is being tested?
VEGF Trap, Bone marrow biopsy and bone marrow aspiration
Type of treatment
Surgery or procedure
How many people
0 participants
Where
No sites listed yet
Study dates
Mar 2007to Oct 2009
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • ECOG performance status 0-2
  • Life expectancy ≥ 60 days
  • AST/ALT ≤ 2.5 times upper limit of normal (ULN)
  • Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
  • Urine protein:creatinine ratio < 1 OR 24-hour urine protein < 500 mg
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception prior to, during, and for at least 6 months after completion of study therapy

Who cannot join

  • Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • Serious or nonhealing wound, ulcer, or bone fracture
  • History of allergic reactions attributed to compounds of similar chemical or biological composition to other agents used in the study
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of treatment
  • Clinically significant cardiovascular disease within the past 6 months, including any of the following:
  • History of cerebrovascular accident
Show all 29Show fewer
  • Myocardial infarction, coronary artery bypass graft, or unstable angina
  • New York Heart Association class III-IV congestive heart failure or serious cardiac arrhythmia requiring medication
  • Clinically significant peripheral vascular disease
  • Pulmonary embolism, deep venous thrombosis, or other thromboembolic event
  • Uncontrolled hypertension, defined as BP > 150/100 mm Hg, or systolic BP > 180 mm Hg if diastolic blood pressure is < 90 mm Hg, on at least 2 repeated determinations on separate days within the past 3 months
  • Evidence of bleeding diathesis or coagulopathy
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements
  • Significant traumatic injury within 28 days prior to day 1 of therapy
  • PRIOR CONCURRENT THERAPY:
  • Recovered from all therapy
  • At least 4 weeks since prior chemotherapy and radiotherapy
  • At least 4 weeks since prior FDA approved agents for treatment of myelodysplastic syndromes and/or AML, including lenalidomide and arsenic trioxide
  • No prior anti-VEGF, anti-VEGFR, or antiangiogenic agents (e.g., bevacizumab)
  • More than 28 days since prior major surgical procedure or open biopsy
  • More than 2 days since prior bone marrow aspirate/biopsy or central venous catheter placement
  • No anticipation of need for major surgical procedure during the study course
  • Full-dose anticoagulation (e.g., warfarin) with PT/INR > 1.5 allowed provided that both of the following criteria are met:
  • In-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant
  • No active bleeding or pathological condition that carries a high risk of bleeding (e.g., known varices)
  • Prior and concurrent hydroxyurea allowed for blast control
  • Hydroxyurea must be discontinued no more than 24 hrs after the first dose of aflibercept
  • No HIV-positive patients on combination antiretroviral therapy
  • No other concurrent investigational agents

About this study

Official title: A Multi-Center Phase 2 Study of Vascular Endothelial Growth Factor (VEGF) Trap as a Single Agent in Acute Myeloid Leukemia

RATIONALE: Aflibercept may stop the growth of cancer cells by blocking blood flow to the cancer.

PURPOSE: This phase II trial is studying how well aflibercept works in treating patients with advanced refractory, relapsed, or untreated acute myeloid leukemia.

Read the detailed description

OBJECTIVES:

Primary

  • To determine the response rate to aflibercept as a single agent in adult patients with advanced refractory, relapsed, or untreated acute myeloid leukemia (AML).
  • To determine the 3-month progression-free survival following treatment with at least 4 courses of aflibercept in these patients.

Secondary

  • To determine if there is any correlation between pre-treatment expression of VEGFR1 or VEGFR2 by marrow myeloblasts and disease response to aflibercept.
  • To determine if bone marrow microvessel density (MVD) pre-treatment correlates with disease response to aflibercept, and if any decrease in MVD following treatment correlates with changes in bone marrow blast percentage (disease response).
  • To assess changes in circulating endothelial cells (CEC) and circulating endothelial progenitor cells (EPC) as pharmacodynamic markers of aflibercept activity and possible correlates of disease response to aflibercept.
  • To measure blood levels of free VEGF versus VEGF bound by aflibercept post-treatment to determine if the chosen dose of aflibercept is sufficient to bind all detectable soluble VEGF in these patients.
  • To characterize the population pharmacokinetics of aflibercept with its associated interpatient variability and to explore for demographic and clinical covariates.
  • To derive individual estimates of the duration over which VEGF-saturating aflibercept concentrations were systematically present and to examine their distribution across the population.
  • To explore the potential relationship between the systemic-free and bound aflibercept levels and safety and efficacy data.

OUTLINE: This is a multicenter study.

Patients receive aflibercept IV over 1 hour on day 1. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo bone marrow and blood sample collection periodically for pharmacokinetic/pharmacodynamic studies. Samples are analyzed for peak plasma-free aflibercept levels after the first infusion, trough plasma-free and bound aflibercept levels prior to each subsequent infusion and 60 days after the last infusion, and anti-aflibercept antibody via ELISA methods; circulating endothelial cells (CEC's) via ELISA and flow cytometry to determine if there is correlation between changes in circulating endothelial cells and changes in bone marrow blast percentage (i.e., disease response); myeloblast expression of VEGFR-1 and VRGFR-2 via immunohistochemistry (IHC); endothelial progenitor cells colony forming units (EPC-CFU's) to determine via in situ staining if changes in circulating endothelial progenitors following treatment with aflibercept correlates with disease response, and if there is a subpopulation of patients identified by pre-treatment circulating EPC-CFU's that may benefit from aflibercept; and bone marrow microvessel density (MVD) determination via immunohistochemistry.

After completion of study treatment, patients are followed for 60 days.

Conditions
Leukemia
Being tested
VEGF Trap, Bone marrow biopsy, bone marrow aspiration, Venipuncture
Keywords
untreated adult acute myeloid leukemia, recurrent adult acute myeloid leukemia
Medical subject headings
Leukemia, Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VEGF TrapBiological

    Also called Vascular endothelial growth factor trap

    Drug under investigation

  • Bone marrow biopsyProcedure or surgery

    To determine response to treatment

  • bone marrow aspirationProcedure or surgery

    Also called Removal of a sample of bone marrow using a needle

    To determine response to treatment

  • VenipunctureProcedure or surgery

    Also called Taking blood sample

    For test of free VEGF Trap compared to bound VEGF Trap and for routine clinical testing during treatment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Response rate of aflibercept

    As determined by the International Working Group: Complete response: bone marrow blast(BMB) percentage (%) <=5% of nucleated cells and no detectable extramedullary disease; Partial response: BMB >5% but decreased by at least 50% pre-treatment (pre-tx) value OR extramedullary disease still present; Stable disease: BMB >5% and decreased or increased by <50% of pre-tx value and no new extramedullary disease; Progressive disease: BMB >=20% and an increase of at least 50% of pre-tx value and/or appearance of at least 50% in circulating blasts

    Measured: day 14 of cycle 4 (14-day cycle)

Secondary outcomes (3)

  1. Bone marrow microvessel density determination at baseline, after courses 2 and 4 of treatment

    Density of microscopically small blood vessels in bone marrow biopsies

    Measured: at baseline, at day 29 and at day 57

  2. Pharmacokinetics of free versus bound VEGF Trap

    Blood levels of free VEGF Trap compared to bound VEGF trap to determine if the chosen level of VEGF Trap is sufficient to bind all detectable soluble VEGF in this group of patients

    Measured: Before and after 1st infusion on day 1, before infusion on day 1 of each 14-day cycle, and 60 days after last dose

  3. Progression-free survival in patients who achieve either a complete or partial response OR stable disease

    Patients who undergo a minimum of 4 cycles of treatment and who have either a complete or partial response to treatment or who have stable disease and who are free of progressive disease at 12 weeks

    Measured: at 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jan 2008 (estimated)
  2. Study startMar 2007
  3. Primary completionMar 2009 (estimated)
  4. Study completionOct 2009

Why it stopped: Another study was opened.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00601991
Sponsor's protocol ID
VICC HEM 0652
Other IDs
P30CA068485, VU-VICC-HEM-0652, VU-VICC-061069
Status last verified
Mar 2013
First submitted
17 Jan 2008
Last updated
2 Apr 2013
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing VEGF Trap, Bone marrow biopsy and bone marrow aspiration in people with Leukemia, run by Vanderbilt-Ingram Cancer Center.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 2 Apr 2013. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Response rate of aflibercept (time frame: day 14 of cycle 4 (14-day cycle)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00601991.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2013.

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