Condition category
Cancer
Date applied
20/12/2005
Date assigned
20/12/2005
Last edited
04/05/2010
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 B. Löwenberg

ORCID ID

Contact details

Erasmus Medical Centre
Daniel den Hoed Cancer Centre
Department of Hematology
P.O. Box 5201
Rotterdam
3008 AE
Netherlands
+31 (0)10 439 1598
b.lowenberg@erasmusmc.nl

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

NTR212; HO43

Study information

Scientific title

Acronym

HOVON 43 AML/SAKK 30/01

Study hypothesis

1. The first hypothesis to be tested is that the outcome in arm B is better than in arm A.
2. The second hypothesis to be tested is that the outcome in arm two is better than in arm one.

Ethics approval

Ethics approval received from the local medical ethics committee

Study design

Prospective randomised, active controlled, parallel group, multicentre trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Condition

Acute Myeloid Leukaemia (AML)

Intervention

Patients will be randomised on entry for induction between:

Arm A:
Cycle I: conventional type daunomycin-cytarabine schedule
Cycle II: intermediate dose cytarabine

Arm B:
Cycle I: daunomycin at escalated dose with standard dose cytarabine
Cycle II: intermediate dose cytarabine

Patients attaining Complete Response (CR) and remaining in CR after cycle II will be randomised between:

Arm one: no further treatment
Arm two: three dosages of Gemtuzumab Ozogamicin (GO, Mylotarg) at four week intervals

For patients with an Human Leukocyte Antigen (HLA) identical sibling donor, an allograft with non-myeloablative conditioning, will be available depending on the active involvement in allotransplantation per centre (optional per centre).

Intervention type

Drug

Phase

Phase III

Drug names

Cytarabine, daunomycin, gemtuzumab ozogamicin

Primary outcome measures

Endpoint for the comparison of induction treatment arm B with arm A:
Event-free survival (i.e. time from registration to induction failure, death or relapse whichever occurs first); the time to failure of patients with induction failure is set at one day.

Endpoint for the comparison of post induction maintenance treatment with GO with no further treatment: disease-free survival measured from the date of second randomisation to relapse or death from any cause.

Secondary outcome measures

Endpoints for the comparison of induction treatment arm B with arm A:
1. Response and especially CR to chemotherapy cycles I and II
2. Overall survival measured form the time of registration
3. Disease-free interval (duration of the first CR) measured from the time of achievement of CR to day of relapse or death from any cause (whichever occurs first)
4. Probability of complete response, relapse, death in CR1, event-free survival, disease-free survival and overall survival will also be assessed in relation to age (61 - 70, 70 - 80, above 80), cytogenetic abnormalities, CD33-positivity of AML (phenotype), P-glycoprotein (PgP) positivity
5. Toxicities and treatment related mortality
6. Time to haematopoietic recovery (Absolute Neutrophil Count [ANC] 0.5 and 1.5 x 10^9/l; platelets 50 and 100 x 10^9/l) after each treatment cycle
7. Number of platelet transfusions and last day of platelet transfusion after each cycle

Endpoints for the comparison of post induction maintenance treatment with GO with no further treatment:
1. Overall survival measured from the date of second randomisation.
2. Probability of relapse and death in first CR from date of second randomisation calculated as competing risks
3. Number and duration of hospitalisation as well as transfusion requirements (red cell and platelet transfusion)

Overall trial start date

09/10/2000

Overall trial end date

01/11/2005

Reason abandoned

Eligibility

Participant inclusion criteria

1. Age 61 years or more
2. Subjects with a cytopathologically confirmed diagnosis of AML (M0-M2 and M4-M7, FAB classification), 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 of greater than or equal to 1.5
3. Subjects with a secondary AML progressing from antecedent Myelodysplasia (MDS) and biphenotypic leukemia are eligible. Antecedent MDS refers to any antecedent haematological disease of at least four month duration
4. World Health Organisation (WHO) performance status less than or equal to two
5. Written informed consent

Participant type

Patient

Age group

Senior

Gender

Both

Target number of participants

800

Participant exclusion criteria

1. Previous induction treatment for AML/MDS
2. Prior chemotherapy within six months of study entry
3. Previous polycythemia rubra vera
4. Primary myelofibrosis
5. Blast crisis of chronic myeloid leukemia
6. AML-FAB type M3 or AML with cytogenetic abnormality t(1517) translocation
7. Impaired hepatic or renal function as defined by:
a. Alanine Aminotransferase (ALT) and/or Aspartate Aminotransferase (AST) greater than 25 x normal value
b. Bilirubin greater than 2 x normal value
8. Serum creatinine greater than 2 x normal value (after adequate hydration), unless these are most likely caused by AML organ infiltration
9. Concurrent severe and/or uncontrolled medical condition (e.g., uncontrolled diabetes, infection, hypertension, etc.,)
10. Cardiac dysfunction as defined by:
10.1. myocardial infarction within the last six months of study entry, or
10.2. reduced left ventricular function with an ejection fraction less than or equal to 50% as measured by Multiple Gated Acquisition (MUGA) scan or echocardiogram (another method for measuring cardiac function is acceptable)
11. Unstable angina
12. Unstable cardiac arrhythmias

Recruitment start date

09/10/2000

Recruitment end date

01/11/2005

Locations

Countries of recruitment

Netherlands

Trial participating centre

Erasmus Medical Centre
Rotterdam
3008 AE
Netherlands

Sponsor information

Organisation

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

Sponsor details

Vrije University Medical Centre (VUMC)
PO Box 7057
Amsterdam
1007 MB
Netherlands
+31 (0)20 444 2693
hdc@hovon.nl

Sponsor type

Research organisation

Website

http://www.hovon.nl/

Funders

Funder type

Research organisation

Funder name

Koningin Wilhelmina Fonds (KWF) (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

1. 2009 results in http://www.ncbi.nlm.nih.gov/pubmed/19776405
2. 2010 results in http://www.ncbi.nlm.nih.gov/pubmed/20103782

Publication citations

  1. Results

    Löwenberg B, Beck J, Graux C, van Putten W, Schouten HC, Verdonck LF, Ferrant A, Sonneveld P, Jongen-Lavrencic M, von Lilienfeld-Toal M, Biemond BJ, Vellenga E, Breems D, de Muijnck H, Schaafsma R, Verhoef G, Döhner H, Gratwohl A, Pabst T, Ossenkoppele GJ, Maertens J, , , , Gemtuzumab ozogamicin as postremission treatment in AML at 60 years of age or more: results of a multicenter phase 3 study., Blood, 2010, 115, 13, 2586-2591, doi: 10.1182/blood-2009-10-246470.

  2. Löwenberg B, Ossenkoppele GJ, van Putten W, Schouten HC, Graux C, Ferrant A, Sonneveld P, Maertens J, Jongen-Lavrencic M, von Lilienfeld-Toal M, Biemond BJ, Vellenga E, van Marwijk Kooy M, Verdonck LF, Beck J, Döhner H, Gratwohl A, Pabst T, Verhoef G, , , , High-dose daunorubicin in older patients with acute myeloid leukemia., N. Engl. J. Med., 2009, 361, 13, 1235-1248, doi: 10.1056/NEJMoa0901409.

Additional files

Editorial Notes