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. - HOVON 81 AM
- Conditions
- Acute myeloid leukaemia (AML), AML FAB M0-M2 or M4-M7diagnosis with refractory anemia with excess of blasts (RAEB) or refractory anemia with excess of blasts in transformation (RAEB-T) with an IPSS score = 1.5MedDRA version: 8.1Level: LLTClassification code 10000886Term: Acute myeloid leukemia
- Registration Number
- EUCTR2006-001777-19-NL
- Lead Sponsor
- HOVON foundation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 200
-Patients > 60 years.
-Patients eligible for standard chemotherapy.
-Patients with a confirmed diagnosis of
*AML FAB M0-M2 or M4-M7 (see appendix A) 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 (see Appendix B)
Subjects with secondary AML progressing from antecedent (at least 4 months duration) myelodysplasia are also eligible.
-SGOT (AST) and SGPT (ALT) = 1.5 x the upper limit of the normal range (ULN) at the laboratory where the analyses were performed.
--Total serum bilirubin level = 1.5 x the ULN at the laboratory where the analysis was performed.
-Serum creatinine concentration = 1.5 x the ULN at the laboratory where the analysis was performed.
-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.
-WHO performance status = 2 (see Appendix G)
-Written informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
-Patients previously treated for AML (any antileukemic therapy including investigational agents)
-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
*in situ carcinoma of the cervix
-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.
-Uncontrolled hypertension
-Patients with a history of non-compliance to medical regimens or who are considered unreliable with respect to compliance
-Patients with any serious concomitant medical condition which could, in the opinion of the investigator, compromise participation in the study.
-Patients who have senile dementia, mental impairment or any other psychiatric disorder that prohibits the patient from understanding and giving informed consent.
-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
-Serious, non-healing wound, ulcer, or bone fracture
-Patients with bleeding diathesis or coagulopathy (unless related to AML)
-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 clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: 1. To assess the safety and tolerability of bevacizumab added to standard induction chemotherapy for AML (frequency and severity of toxicities and the durations of neutropenia and thrombocytopenia)<br>2. To assess in a randomized comparison the effect of bevacizumab on the CR rate.;Secondary Objective: 1. To determine the efficacy profile (event free survival and disease free survival) associated with the two therapy regimens.<br>2. To measure MRD by immunophenotyping in relation to clinical response parameters.<br>3. To determine micro vascular density after the first course of therapy in both treatment arms.<br>4. To measure VEGF levels in plasma and VEGF receptors on leukemic blasts in relation to clinical parameters.<br>;Primary end point(s): - Incidence of DLT<br>- The effect of Bevacizumab on the CR rate.<br>
- Secondary Outcome Measures
Name Time Method