Aflibercept in Treating Patients With Myelodysplastic Syndromes

NCT00509249 | Terminated Phase 2 Results DMC

• 4 other identifiers: NCI-2009-00180PHII-73N01CM62209CDR0000558101
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 3 years

Study Arms (1)

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.

Biological: ziv-aflibercept; Other: laboratory biomarker analysis; Other: pharmacological study

Interventions

ziv-aflibercept BIOLOGICAL

Given IV

Also known as: aflibercept, vascular endothelial growth factor trap, VEGF Trap, Zaltrap

Arm I

laboratory biomarker analysis OTHER

Correlative studies

Arm I

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Arm I

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Leukemia, Myelomonocytic, Chronic; Myeloproliferative Disorders

Interventions

aflibercept

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Study was terminiated after completion of the first stage due to a lack of activity (no hematological responses were observed).

Results Point of Contact

• Title: DCC Project Administrator
• Organization: California Cancer Consortium

CCCP@coh.org

626-256-4673

Study Officials

• Mark Kirschbaum

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2007
• First Posted: July 31, 2007
• Study Start: September 1, 2007
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: January 8, 2015
• Results First Posted: January 8, 2015

Record last verified: 2012-11

Locations

US (1)