Condition category
Cancer
Date applied
07/03/2007
Date assigned
07/03/2007
Last edited
03/10/2007
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

http://www.hovon.nl

Contact information

Type

Scientific

Primary contact

Prof G J Ossenkoppele

ORCID ID

Contact details

VU Medical Centre (VUMC)
Afd. Hematologie
P.O. Box 7057
Amsterdam
1007 NL
Netherlands
+31 (0)20 444 2604
g.ossenkoppele@vumc.nl

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

HO81

Study information

Scientific title

Acronym

HOVON 81 AML

Study hypothesis

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

Approval received from the local medical ethics committee (Medische Ethische Toetsingscommissie VU Medisch Centrum) on the 7th December 2006 (ref: 2006/215).

Study design

Randomised, active controlled, parallel group, multicentre trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

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

Phase

Phase II

Drug names

Daunorubicine/cytarabine-arabinoside and bevacizumab

Primary outcome measures

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 trial start date

13/02/2007

Overall trial end date

01/10/2008

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Senior

Gender

Not Specified

Target number of participants

200

Participant 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

Recruitment start date

13/02/2007

Recruitment end date

01/10/2008

Locations

Countries of recruitment

Netherlands

Trial participating centre

VU Medical Centre (VUMC)
Amsterdam
1007 NL
Netherlands

Sponsor information

Organisation

Dutch Haemato-Oncology Association (Stichting Hemato-Oncologie Volwassenen Nederland) (HOVON) (The Netherlands)

Sponsor details

Erasmus Medical Centre
Daniel den Hoed Kliniek
P.O. Box 5201
Rotterdam
3008 AE
Netherlands
+31 (0)10 439 1568
hdc@erasmusmc.nl

Sponsor type

Research organisation

Website

http://www.hovon.nl

Funders

Funder type

Research organisation

Funder name

Dutch Haemato-Oncology Association (Stichting Hemato-Oncologie Volwassenen Nederland) (HOVON) (The Netherlands)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Koningin Wilhelmina Fonds (KWF) (The Netherlands)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes