Condition category
Cancer
Date applied
19/12/2005
Date assigned
19/12/2005
Last edited
13/11/2008
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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

Sponsor information

Organisation

Novartis Pharma AG (Switzerland)

Sponsor details

-
Basel
CH-4002
Switzerland

Sponsor type

Industry

Website

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

  1. 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.

Additional files

Editorial Notes