A phase II multicentre study to assess the tolerability and efficacy of the addition of bevacizumab to standard induction therapy in Acute Myeloid Leukaemia and high risk myelodysplastic syndrome above 60 years
| ISRCTN | ISRCTN18332222 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN18332222 |
| EudraCT/CTIS number | 2006-001777-19 |
| Secondary identifying numbers | HO81 |
- Submission date
- 07/03/2007
- Registration date
- 07/03/2007
- Last edited
- 19/07/2021
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English summary of protocol
Not provided at time of registration
Contact information
Prof G J Ossenkoppele
Scientific
Scientific
VU Medical Centre (VUMC)
Afd. Hematologie
P.O. Box 7057
Amsterdam
1007 NL
Netherlands
| Phone | +31 (0)20 444 2604 |
|---|---|
| g.ossenkoppele@vumc.nl |
Study information
| Study design | Randomised, active controlled, parallel group, multicentre trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Scientific title | A phase II multicentre study to assess the tolerability and efficacy of the addition of bevacizumab to standard induction therapy in Acute Myeloid Leukaemia and high risk myelodysplastic syndrome above 60 years |
| Study acronym | HOVON 81 AML |
| Study objectives | 1. Evaluation of the safety and tolerability of bevacizumab added to standard induction chemotherapy 2. Evaluation of the effect of bevacizumab on the Complete Response (CR) rate The hypothesis to be tested is that arm B is tolerable and that the outcome in arm B is better than in arm A. |
| Ethics approval(s) | Approval received from the local medical ethics committee (Medische Ethische Toetsingscommissie VU Medisch Centrum) on the 7th December 2006 (ref: 2006/215). |
| Health condition(s) or problem(s) studied | Myeloid Leukaemia |
| Intervention | Patients will be randomised on entry between: Arm A: Cycle I: daunorubicine/cytarabine-arabinoside Cycle II: intermediate dose cytarabine-arabinoside. Arm B: Cycle I: daunorubicine/cytarabine-arabinoside and two doses of bevacizumab 5 or 10 mg/kg Cycle II: intermediate dose cytarabine-arabinoside and two doses of bevacizumab 5 or 10 mg/kg |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Daunorubicine/cytarabine-arabinoside and bevacizumab |
| Primary outcome measure | Incidence of Dose-Limiting Toxicity (DLT) and the effect of bevacizumab on the CR-rate. |
| Secondary outcome measures | 1. Overall survival (time from registration until the death of the patient) 2. Event free survival (i.e., time from registration to induction failure, death or relapse whichever occurs first) 3. Minimum Residual Disease (MRD) percentage |
| Overall study start date | 13/02/2007 |
| Completion date | 01/10/2008 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Senior |
| Sex | Not Specified |
| Target number of participants | 200 |
| Key inclusion criteria | 1. Patients greater than 60 years 2. Patients eligible for standard chemotherapy 3. Patients with a confirmed diagnosis of Acute Myeloid Leukaemia (AML) French-American-British (FAB) classification M0 - M2 or M4 - M7 or with Refractory Anaemia with Excess of Blasts (RAEB) or Refractory Anaemia with Excess of Blasts in Transformation (RAEB-T) with an International Prognostic Scoring System (IPSS) score greater than or equal to 1.5 4. Subjects with secondary AML progressing from antecedent (at least four months duration) myelodysplasia are also eligible. 5. Serum Glutamic Oxaloacetic Transaminase (SGOT) (Aspartate aminotransferase [AST]) and Serum Glutamic Pyruvic Transaminase (SGPT) (Alanine Aminotransferase [ALT]) less than or equal to 1.5 x the Upper Limit of the Normal range (ULN) at the laboratory where the analyses were performed 6. Total serum bilirubin level less than or equal to 1.5 x the ULN at the laboratory where the analysis was performed 7. Serum creatinine concentration less than or equal to 1.5 x the ULN at the laboratory where the analysis was performed 8. Proteinuria at baseline: urine dipstick of proteinuria less than 2+. Patients discovered to have greater than or equal to 2+ proteinuria on dipstick urinalysis at baseline, should undergo a 24-hour urine collection and must demonstrate less than or equal to 1 g of protein/24 hr 9. World Health Organisation (WHO) performance status less than or equal to two 10. Written informed consent |
| Key exclusion criteria | 1. Patients previously treated for AML (any anti-leukaemic therapy including investigational agents) 2. Past or current history (within the last two years prior to randomisation) 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 (less than or equal to six months prior to randomisation), myocardial infarction (less than or equal to six months prior to randomisation), 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 less than 50% as evaluated by echocardiogram or Multiple Gated Acquisition (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 humanised antibodies or to any excipients of bevacizumab formulation; or to any other study drugs |
| Date of first enrolment | 13/02/2007 |
| Date of final enrolment | 01/10/2008 |
Locations
Countries of recruitment
- Netherlands
Study participating centre
VU Medical Centre (VUMC)
Amsterdam
1007 NL
Netherlands
1007 NL
Netherlands
Sponsor information
Dutch Haemato-Oncology Association (Stichting Hemato-Oncologie Volwassenen Nederland) (HOVON) (The Netherlands)
Research organisation
Research organisation
Erasmus Medical Centre
Daniel den Hoed Kliniek
P.O. Box 5201
Rotterdam
3008 AE
Netherlands
| Phone | +31 (0)10 439 1568 |
|---|---|
| hdc@erasmusmc.nl | |
| Website | http://www.hovon.nl |
"ROR" |
https://ror.org/056kpdx27 |
Funders
Funder type
Research organisation
Dutch Haemato-Oncology Association (Stichting Hemato-Oncologie Volwassenen Nederland) (HOVON) (The Netherlands)
No information available
Koningin Wilhelmina Fonds (KWF) (The Netherlands)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Editorial Notes
19/07/2021: EudraCT number added.
