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 |
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DOI | https://doi.org/10.1186/ISRCTN77039377 |
Secondary identifying numbers | NTR212; HO43 |
- 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
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 |
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b.lowenberg@erasmusmc.nl |
Study information
Study design | Prospective randomised, active controlled, parallel group, multicentre trial |
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Primary study design | Interventional |
Secondary study design | Randomised controlled trial |
Study setting(s) | Not specified |
Study type | Treatment |
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 |
Pharmaceutical study type(s) | |
Phase | Phase III |
Drug / device / biological / vaccine name(s) | Cytarabine, daunomycin, gemtuzumab ozogamicin |
Primary outcome measure | 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 study start date | 09/10/2000 |
Completion date | 01/11/2005 |
Eligibility
Participant type(s) | Patient |
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Age group | Senior |
Sex | Both |
Target number of participants | 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
3008 AE
Netherlands
Sponsor information
Dutch Haemato-Oncology Association (Stichting Hemato-Oncologie Volwassenen Nederland) (HOVON) (Netherlands)
Research organisation
Research organisation
Vrije University Medical Centre (VUMC)
PO Box 7057
Amsterdam
1007 MB
Netherlands
Phone | +31 (0)20 444 2693 |
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hdc@hovon.nl | |
Website | http://www.hovon.nl/ |
https://ror.org/056kpdx27 |
Funders
Funder type
Research organisation
Koningin Wilhelmina Fonds (KWF) (Netherlands)
No information available
Results and Publications
Intention to publish date | |
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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 |
Study outputs
Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
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Plain English results | No | Yes | |||
Results article | results | 24/09/2009 | Yes | No | |
Results article | results | 01/04/2010 | Yes | No |
Editorial Notes
19/10/2018: Cancer Research UK lay results summary link added to Results (plain English)