Atypical Chronic Myeloid Leukemia, BCR-ABL1 NegativePhase 2NCT00509249
Aflibercept in Treating Patients With Myelodysplastic Syndromes
A Phase 2 study testing ziv-aflibercept, laboratory biomarker analysis and pharmacological study in people with Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative and Chronic Myelomonocytic Leukemia, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative, Chronic Myelomonocytic Leukemia, de Novo Myelodysplastic Syndromes
- What is being tested?
- ziv-aflibercept, laboratory biomarker analysis and pharmacological study
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2007to Dec 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
City of Hope Medical Center
Duarte, California, 91010
About this study
Official title: A Phase II Study of VEGF Trap (NSC 724770) in Patients With MDS
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
Read the detailed description
OBJECTIVES:
- 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.
- Conditions
- 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
- Being tested
- ziv-aflibercept, laboratory biomarker analysis, pharmacological study
- Medical subject headings
- Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative, Leukemia, Myelomonocytic, Chronic, Myeloproliferative Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ziv-afliberceptBiological
Also called aflibercept, vascular endothelial growth factor trap, VEGF Trap, Zaltrap
Given IV
laboratory biomarker analysisOther
Correlative studies
Also called pharmacological studies
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | 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. Receives: Biological: ziv-aflibercept; Other: laboratory biomarker analysis; Other: pharmacological study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hematological Response Rate
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.
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2007 (estimated)
- Study startSep 2007
- Primary completionDec 2010
- Study completionDec 2010
Why it stopped: Early termination for discouraging results
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Atypical Chronic Myeloid Leukemia, BCR-ABL1 NegativeStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Mark Kirschbaum, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00509249
- Sponsor's protocol ID
- NCI-2009-00180
- Other IDs
- PHII-73, N01CM62209, CDR0000558101
- Status last verified
- Nov 2012
- First submitted
- 30 Jul 2007
- Last updated
- 8 Jan 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of VEGF Trap (NSC 724770) in Patients With MDS
- ClinicalTrials.gov ID
- NCT00509249
- Acronym / sponsor ID
- NCI-2009-00180
- Conditions
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Early termination for discouraging results
- Enrolment
- 18 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Sep 2007
- Primary completion
- Dec 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 31 Jul 2007 (estimated)
- Results
- Posted 8 Jan 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
OBJECTIVES:
- 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Biological: ziv-aflibercept, Other: laboratory biomarker analysis, Other: pharmacological studyPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Patients must have histologically or cytologically confirmed myelodysplastic syndromes (MDS), including any of the following:
- 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
Key exclusion criteria (24 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ziv-afliberceptAlso: aflibercept, vascular endothelial growth factor trap, VEGF Trap, ZaltrapGiven IV | Biological | Arm I |
| laboratory biomarker analysisCorrelative studies | Other | Arm I |
| pharmacological studyAlso: pharmacological studiesCorrelative studies | Other | Arm I |
Primary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Kirschbaum principal investigator
City of Hope Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ziv-aflibercept, laboratory biomarker analysis and pharmacological study in people with Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative and Chronic Myelomonocytic Leukemia, run by National Cancer Institute (NCI) at 1 site in United States.
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 19 inclusion and 24 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: stopped early, as of the sponsor's last update on 8 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Yes. Results are posted in the registry (first posted 8 Jan 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Hematological Response Rate (time frame: Up to 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Jan 2015.