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