Randomised induction and post induction therapy in older patients (greater than or equal to 61 years of age) with Acute Myelocytic Leukaemia (AML) and Refractory Anaemia with Excess of Blasts (RAEB, RAEB-t)

ISRCTN	ISRCTN77039377
DOI	https://doi.org/10.1186/ISRCTN77039377
Protocol serial number	NTR212; HO43
Sponsor	Dutch Haemato-Oncology Association (Stichting Hemato-Oncologie Volwassenen Nederland) (HOVON) (Netherlands)
Funder	Koningin Wilhelmina Fonds (KWF) (Netherlands)

Submission date: 20/12/2005
Registration date: 20/12/2005
Last edited: 19/10/2018

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof B. Löwenberg
Scientific

Erasmus Medical Centre
Daniel den Hoed Cancer Centre
Department of Hematology
P.O. Box 5201
Rotterdam
3008 AE
Netherlands

Phone	+31 (0)10 439 1598
Email	b.lowenberg@erasmusmc.nl

Study information

Primary study design	Interventional
Study design	Prospective randomised, active controlled, parallel group, multicentre trial
Secondary study design	Randomised controlled trial
Scientific title	Randomised induction and post induction therapy in older patients (greater than or equal to 61 years of age) with Acute Myelocytic Leukaemia (AML) and Refractory Anaemia with Excess of Blasts (RAEB, RAEB-t)
Study acronym	HOVON 43 AML/SAKK 30/01
Study objectives	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(s)	Ethics approval received from the local medical ethics committee
Health condition(s) or problem(s) studied	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 / device / biological / vaccine name(s)	Cytarabine, daunomycin, gemtuzumab ozogamicin
Primary outcome measure(s)	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.
Key secondary outcome measure(s)	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)
Completion date	01/11/2005

Eligibility

Participant type(s)	Patient
Age group	Senior
Sex	All
Target sample size at registration	800
Key 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
Key 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
Date of first enrolment	09/10/2000
Date of final enrolment	01/11/2005

Locations

Countries of recruitment

Netherlands

Study participating centre

Erasmus Medical Centre

Rotterdam
3008 AE
Netherlands

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	24/09/2009		Yes	No
Results article	results	01/04/2010		Yes	No
Plain English results				No	Yes
Study website	Study website	11/11/2025	11/11/2025	No	Yes

Editorial Notes

19/10/2018: Cancer Research UK lay results summary link added to Results (plain English)