|- candidate number||2462|
|- NTR Number||NTR904|
|- Date ISRCTN created||7-mrt-2007|
|- date ISRCTN requested||6-mrt-2007|
|- Date Registered NTR||13-feb-2007|
|- Secondary IDs||HO81 |
|- Public Title||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.|
|- Scientific Title||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.|
|- ACRONYM||HOVON 81 AML|
|- hypothesis||The hypothesis to be tested is that arm B is tolerable and that the outcome in arm B is better than in arm A.|
|- Healt Condition(s) or Problem(s) studied||Acute Myeloid Leukemia (AML), Refractory anemia with excess of blasts (RAEB-t), Refractory anemia with excess of blasts in transformation (RAEB-t)|
|- 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.|
|- mec approval received||yes|
|- multicenter trial||yes|
|- planned startdate ||13-feb-2007|
|- planned closingdate||1-okt-2008|
|- Target number of participants||200|
|- Interventions||Patients will be randomized on entry between:
Arm A: Cycle I: daunorubicine/cytarabine-arabinoside. Cycle II: intermediate dose cytarabine-arabinoside.
Or Arm B: Cycle I: daunorubicine/cytarabine-arabinoside and 2 doses of bevacizumab 5 or 10 mg/kg. Cycle II: intermediate dose cytarabine-arabinoside and 2 doses of bevacizumab 5 or 10 mg/kg|
|- Primary outcome||Incidence of DLT and the effect of bevacizumab on the CR-rate|
|- Secondary outcome||1. Overall survival (time from registration till the death of the patient);
2. Event free survival (i.e., time from registration to induction failure, death or relapse whichever occurs first);
3. MRD percentage|
|- Trial web site||http://www.hovon.nl|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES||Prof. Dr. G.J. Ossenkoppele|
|- CONTACT for SCIENTIFIC QUERIES||Prof. Dr. G.J. Ossenkoppele|
|- Sponsor/Initiator ||HOVON Data Center|
(Source(s) of Monetary or Material Support)
|Koningin Wilhelmina Fonds (KWF), HOVON|
|- Brief summary||Study phase: Phase II
Study objective: Evaluation of the safety and tolerability of Bevacizumab added to standard induction chemotherapy. Evaluation of the effect of Bevacizumab on the CR rate
Patient population: Patients with AML (except FAB M3), RAEB or RAEB-t with IPSS ¡Ý 1.5, previously untreated, age > 60 yrs.
Study design: Prospective, multicenter, open-label, with randomization between standard induction chemotherapy with or without Bevacizumab.The initial Bevacizumab dose is 5 mg/kg i.v. on day 1+15 of each cycle. Decisions regarding dose escalation to 10 mg/kg, continuation with dose level 5 mg/kg, or stopping, are based on the incidence of DLT (dose limiting toxicity: death within 30 days of start cycle I and before start cycle II)Duration of treatment: Expected duration of 2 cycles of induction chemotherapy with of without Bevacizumab including evaluation is about 3 months.|
|- Main changes (audit trail)|
|- RECORD||13-feb-2007 - 7-mrt-2007|