Aflibercept in Treating Patients With Myelodysplastic Syndromes
Condition: 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
MeSH terms: Leukemia; Preleukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Myelodysplastic Syndromes; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Syndrome
Intervention: ziv-aflibercept; laboratory biomarker analysis; pharmacological study
Intervention description: Given IV; Correlative studies; Correlative studies
Intervention MeSH terms: Aflibercept; Endothelial Growth Factors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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
    

Eligibility criteria:

        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