Contact information
Type
Scientific
Primary contact
Prof B. Löwenberg
ORCID ID
Contact details
Erasmus Medical Center
Daniel den Hoed Cancer Center
Department of Hematology
P.O. Box 5201
Rotterdam
3008 AE
Netherlands
+31 (0)10 4391598
b.lowenberg@erasmusmc.nl
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
HO31; NTR360
Study information
Scientific title
Acronym
HOVON 31 AML/Novartis PSC C 302-E-00
Study hypothesis
Evaluation of the effect of PSC-833 during induction treatment with daunorubicin and cytarabine.
Ethics approval
Received from the local medical ethics committee
Study design
Multicentre, open label, randomised, active controlled, parallel group study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
Acute myeloid leukaemia (AML)
Intervention
Patients with AML, meeting all eligibility criteria will be randomised on entry between:
Arm A: two induction cycles of daunorubicin (DNR) 45 mg/m^2/day, days 1 - 3 and cytarabine (Ara-C) 200 mg/m^2/day, days 1 - 7, or
Arm B: two induction cycles of DNR 35 mg/m^2/day, days 1 - 3; Ara-C 200 mg/m^2/day, days 1 - 7; and PSC-833 loading dose 2 mg/kg over 2 hours, followed by 10 mg/kg/day, days 1 - 3
Patients in CR will then be given one consolidation cycle without PSC-833 consisting of Ara-C, mitoxantrone and etoposide.
Intervention type
Drug
Phase
Not Specified
Drug names
Daunorubicin, cytarabine, PSC-833
Primary outcome measures
Event-free survival
Secondary outcome measures
1. Complete remission
2. Disease-free survival
3. Overall survival
4. Association between complete remission and expression of P-gp by AML-blasts
Overall trial start date
12/05/1997
Overall trial end date
17/02/1999
Reason abandoned
Eligibility
Participant inclusion criteria
1. Aged greater than or equal to 60 years
2. Subjects who have a cytopathologically confirmed diagnosis of previously untreated AML (M0-M2 and M4-M7, FAB classification)
3. Subjects with secondary AML progressing from antecedent MDS are eligible if there has been no previous chemotherapy. Antecedent MDS is defined as any antecedent haematological disease of at least 4 months duration.
4. World Health Organization (WHO) performance status less than or equal to 2
5. Subjects have given written informed consent
Participant type
Patient
Age group
Senior
Gender
Both
Target number of participants
400
Participant exclusion criteria
1. Cytopathologically confirmed central nervous system (CNS) infiltration. NB: in the absence of clinical suspicion of CNS involvement, lumbar puncture is not required.
2. Subjects have had previous Polycythemia Rubra Vera, primary myelofibrosis, are in blast cell crisis of chronic myeloid leukaemia or are M3 AML according to FAB classification
3. Subject has neurosensory toxicity greater than or equal to Grade 2 (NCIC Expanded CTC)
4. Subject has neurocerebellar toxicity greater than or equal to Grade 1 (NCIC Expanded CTC)
5. Subject is known to be positive for human immunodeficiency virus (HIV) type 1 antibody (testing to determine HIV antibody status is not necessary to be eligible)
6. Subject has impairment of hepatic or renal function as defined by the following baseline laboratory values:
6.1. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) greater than or equal to 2.5 times IULN
6.2. Alkaline phosphatase greater than or equal to 2.5 times IULN
6.3. Serum total bilirubin greater than or equal to 1.5 times IULN
6.4. Serum creatinine greater than or equal to 1.5 times IULN after adequate hydration
7. Subject is currently receiving treatment with any of the agents listed in the protocol if treatment cannot be discontinued at the specified time relative to PSC-833 administration. All of the drugs listed are well substantiated to interact with cyclosporin A.
8. Subject has had major surgery within 2 weeks of study entry
9. Subject has received investigational therapy within 30 days of study entry
10. Subject has known hypersensitivity to cyclosporin A
11. Subject has received prior radiotherapy within 4 weeks of study entry
12. Subject is less than 5 years free of another primary malignancy with the exception of basal cell carcinoma of the skin and stage 1 cervical carcinoma
13. Subject has previously been treated with chemotherapy for AML
14. Subject has concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension etc.)
15. Subject has a psychological, intellectual or sensory dysfunction which is likely to impede their ability to understand and comply with study requirements
16. Subject had a myocardial infarction within the last 6 months, has symptomatic ischaemic heart disease, congestive heart failure or other uncontrolled coronary disease
Recruitment start date
12/05/1997
Recruitment end date
17/02/1999
Locations
Countries of recruitment
Netherlands
Trial participating centre
Erasmus Medical Center
Rotterdam
3008 AE
Netherlands
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
Novartis Pharma B.V. (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
Results in http://www.ncbi.nlm.nih.gov/pubmed/15994288
Publication citations
-
Results
van der Holt B, Löwenberg B, Burnett AK, Knauf WU, Shepherd J, Piccaluga PP, Ossenkoppele GJ, Verhoef GE, Ferrant A, Crump M, Selleslag D, Theobald M, Fey MF, Vellenga E, Dugan M, Sonneveld P, The value of the MDR1 reversal agent PSC-833 in addition to daunorubicin and cytarabine in the treatment of elderly patients with previously untreated acute myeloid leukemia (AML), in relation to MDR1 status at diagnosis., Blood, 2005, 106, 8, 2646-2654, doi: 10.1182/blood-2005-04-1395.