A Trial of Bevacizumab in Myelodysplastic Syndromes (Int-1, Int-2 and High Risk According to International Prognostic Scoring System (IPSS)) With Excess of Marrow Blasts

This is an interventional treatment trial for Myelodysplastic Syndromes focused on measuring Myelodysplastic syndromes (int-1, int-2 and high risk according to IPSS) with excess of marrow blasts including CMML with leucocytes<10 000/mm3 Read More

Inclusion Criteria:

• MDS patient with excess of marrow blasts (≥ 5%) including RAEB, RAEB-t and CMML with leucocytes < 10 000/mm3 according to FAB classification
• IPSS int-1, int-2 or high
• Age > 60 years (younger adults may be included, but only in the absence of donor for allogeneic stem cell transplantation, and if contra-indication to intensive chemotherapy)
• No previous allogeneic SCT or intensive anthracycline-Ara C chemotherapy.

• Adequate renal function:

  • Serum creatinine ≤ 1.25 x ULN or calculated creatinine clearance ≥ 50 mL/min AND
  • Urine dipstick for proteinuria < 2+. Patients discovered to have ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1 g of protein in 24 hours

• Adequate liver function:

  • Total bilirubin < 1.5 x upper limit of normal (ULN) AND Asparagine aminotransferase (AST), alanine aminotransferase (ALT) < 2.5 x ULN in patients without liver metastases
• International normalised ratio (INR) ≤1.5 and prothrombin time (PPT) ≤ 1.5 x ULN within 7 days prior to enrolment
• If female, should not be pregnant or breast-feeding. Women with an intact uterus (unless amenorrhoeic for the last 24 months) must have a negative serum pregnancy test within 28 days prior to enrollment into the study. If a serum pregnancy test is not performed within 7 days prior to the first dose of bevacizumab, a confirmatory urine test (within 7 days prior to the first dose of bevacizumab) is required.
• Life expectancy ≥ 6 months
• Patient with health insurance
• Written informed consent

Exclusion Criteria:

• Therapy related MDS (after chemo or radiotherapy) for a previous neoplasm or other disease including AML
• A preexisting thrombocytopenia < 20 000/mm3
• Major surgery (including open biopsy), significant traumatic injury within 28 days prior to enrolment or anticipation of the need for major surgery during study treatment
• Minor surgery, including insertion of an indwelling catheter, within 24 hours prior to the first bevacizumab infusion
• Prior tumor (except localized cervix carcinoma or cutaneous basal cell carcinoma) unless in remission for at least 3 years.
• Uncontrolled diabetes mellitus
• Current or recent (within 10 days of first dose of bevacizumab) use of aspirin (> 325 mg/day)
• Uncontrolled hypertension (blood pressures: systolic > 150 mmHg and/or diastolic > 100 mmHg)
• Clinically significant (i.e., active) cardiovascular disease for example CVA (≤6 months before enrollment), myocardial infarction (≤ 6 months before enrollment), unstable angina, congestive heart failure NYHA Class ≥ II, serious cardiac arrhythmia requiring medication during the study and might interfere with regularity of the study treatment, or not controlled by medication
• Non-healing wound, active peptic ulcer or bone fracture
• History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months of enrolment
• Women with an intact uterus (unless amenorrhoeic for the last 24 months) not using effective, non-hormonal means of contraception (intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) during the study and for a period of 6 months following the last administration of bevacizumab. Men who do not agree to use effective contraception during the study and for a period of 60 days following the last administration of bevacizumab
• Investigational treatment for MDS within 6 weeks of treatment onset
• Patients unable to give informed consent or to be followed up adequately
• Known hypersensitivity to a product from Chinese Hamster Ovary mammalian cell or to a recombinant humanized monoclonal antibody