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A Phase II multicenter study to assess the tolerability and efficacy of the addition of Bevacizumab to standard induction therapy in AML and high risk MDS above 60 years.

Recruiting
Conditions
Acute Myeloid leukemia (AML), RAEB(-t)
Registration Number
NL-OMON20893
Lead Sponsor
Stichting Hemato-Oncologie voor Volwassenen Nederland (HOVON) P/a HOVON Data CenterErasmus MC - Daniel den HoedPostbus 52013008 AE RotterdamTel: 010 4391568Fax: 010 4391028e-mail: hdc@erasmusmc.nl
Brief Summary

/A

Detailed Description

Not available

Recruitment & Eligibility

Status
Recruiting
Sex
Not specified
Target Recruitment
200
Inclusion Criteria

1. Patients > 60 years.
2. Patients eligible for standard chemotherapy.
3. Patients with a confirmed diagnosis of AML FAB M0-M2 or M4-M7 or with refractory anemia with excess of blasts (RAEB) or refractory anemia with excess of blasts in transformation (RAEB-T) with an IPSS score >= 1.5
4. Subjects with secondary AML progressing from antecedent (at least 4 months duration) myelodysplasia are also eligible.
5. SGOT (AST) and SGPT (ALT) <= 1.5 x the upper limit of the normal range (ULN) at the laboratory where the analyses were performed.
6. Total serum bilirubin level <= 1.5 x the ULN at the laboratory where the analysis was performed.
7. Serum creatinine concentration <= 1.5 x the ULN at the laboratory where the analysis was performed.
8. Proteinuria at baseline: Urine dipstick of 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/24 hr.
9. WHO performance status <= 2
10. Written informed consent.

Exclusion Criteria

1. Patients previously treated for AML (any antileukemic therapy including investigational agents)
2. Past or current history (within the last 2 years prior to randomization) of malignancies except for the indication under this study and curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix
3. Clinically significant (i.e. active) cardiovascular disease, for example cerebrovascular accidents (<= 6 months prior to randomization), myocardial infarction (<= 6 months prior to randomization), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, reduced left ventricular ejection fraction of < 50% as evaluated by echocardiogram or MUGA scan.
4. Uncontrolled hypertension
5. Patients with a history of non-compliance to medical regimens or who are considered unreliable with respect to compliance
6. Patients with any serious concomitant medical condition which could, in the opinion of the investigator, compromise participation in the study.
7. Patients who have senile dementia, mental impairment or any other psychiatric disorder that prohibits the patient from understanding and giving informed consent.
8. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study
9. Serious, non-healing wound, ulcer, or bone fracture
10. Patients with bleeding diathesis or coagulopathy (unless related to AML)
11. Patients with known allergy to Chinese hamster ovary cell proteins or other recombinant human or humanized antibodies or to any excipients of bevacizumab formulation; or to any other study drugs.

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Incidence of DLT and the effect of bevacizumab on the CR-rate
Secondary Outcome Measures
NameTimeMethod
1. Overall survival (time from registration till the death of the patient);<br>2. Event free survival (i.e., time from registration to induction failure, death or relapse whichever occurs first);<br>3. MRD percentage
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