Contact information
Type
Scientific
Primary contact
Dr H M Lokhorst
ORCID ID
Contact details
University Medical Centre Utrecht
Department of Haematology
PO Box 85500
Utrecht
3508 GA
Netherlands
+31 (0)30 250 7230
h.lokhorst@digd.azu.nl
Additional identifiers
EudraCT number
ClinicalTrials.gov number
NCT00028886
Protocol/serial number
HO50
Study information
Scientific title
A randomised phase III study on the effect of thalidomide combined with Adriamycin®, dexamethasone and high dose melphalan in patients with multiple myeloma
Acronym
HOVON 50 MM/GMMG-HD3
Study hypothesis
Study objectives:
Evaluation of the effect of thalidomide in addition to Adriamycin, Dexamethasone (AD) and high dose melphalan.
The hypothesis to be tested is that the outcome in arm B is better than in arm A.
Ethics approval
Ethics approval received from the local medical ethics committee
Study design
Multicentre randomised active controlled parallel group trial
Primary study design
Interventional
Secondary study design
Randomised parallel trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use contact details to request a participant information sheet
Condition
Multiple myeloma
Intervention
Patients with multiple myeloma, meeting all eligibility criteria will be randomised on entry between:
Arm A: Standard Vincristine, Adriamycin and Dexamethasone (VAD) induction, followed by intensive chemotherapy with High-dose Melphalan, followed by maintenance therapy with alpha-interferon
Arm B: Induction chemotherapy with Thalidomide, Adriamycin and Dexamethasone (TAD) followed by intensive chemotherapy with High-dose Melphalan, followed by maintenance with Thalidomide
Intervention type
Drug
Phase
Phase III
Drug names
Standard Vincristine, Doxorubicin (Adriamycin®) and Dexamethasone (VAD) induction, thalidomide, Adriamycin®, dexamethasone, melphalan, alpha-interferon
Primary outcome measures
Event-free survival (i.e. time from registration to induction failure, progression or death, whichever occurs first); the time to failure of patients with induction failure is set at one day. Patients are considered induction failure when they have not achieved at least a Partial response (PR) and are not eligible for further treatment according to protocol.
Secondary outcome measures
1. Response (PR and Complete Response [CR])
2. Overall survival measured form the time of registration. Patient still alive or lost to follow up are censored at the date they were last known to be alive
3. Progression free survival (duration of the first response [PR or CR]) measured from the time of achievement of PR (or CR) to date of progression or death from any cause (whichever occurs first)
4. Toxicities of thalidomide and chemotherapy
Overall trial start date
27/11/2001
Overall trial end date
01/06/2005
Reason abandoned
Eligibility
Participant inclusion criteria
1. Patients with a confirmed diagnosis of multiple myeloma stage II or III according to the Salmon and Durie criteria
2. Age 18 to 65 years inclusive
3. World Health Organisation (WHO) performance status zero to three
4. Negative pregnancy test at inclusion if applicable
5. Written informed consent
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
450
Participant exclusion criteria
1. Known intolerance to thalidomide
2. Systemic AL amyloidosis
3. Previous chemotherapy or radiotherapy except two cycles of melphalan/prednisone or local radiotherapy in case of local myeloma progression
4. Severe cardiac dysfunction (New York Heart Association [NYHA] classification II to IV)
5. Significant hepatic dysfunction (serum bilirubin greater than or equal to 30 micromol/l or transaminases greater than or equal to 25 times normal level), unless related to myeloma
6. Patients known to be Human Immunodeficiency Virus (HIV)-positive
7. Patients with active, uncontrolled infections
8. Patients with a history of active malignancy during the past five years with the exception of basal carcinoma of the skin or stage 0 cervical carcinoma
9. Patients who are not willing or capable to use adequate contraception during the therapy (all men, all pre-menopausal women)
10. Patients less than or equal to 55 years with a Human Leukocyte Antigen (HLA)-identical sibling who will undergo myeloablative Allogeneic Stem Cell Transplantation (AlloSCT)
Recruitment start date
27/11/2001
Recruitment end date
01/06/2005
Locations
Countries of recruitment
Netherlands
Trial participating centre
University Medical Centre Utrecht
Utrecht
3508 GA
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
Funders
Funder type
Research organisation
Funder name
Dutch Haemato-Oncology Association (Stichting Hemato-Oncologie Volwassenen Nederland) (HOVON) (Netherlands)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
The National Cancer Fund (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
2003 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/12845480
2007 results in: http://www.ncbi.nlm.nih.gov/pubmed/17377586
2010 results in: http://www.ncbi.nlm.nih.gov/pubmed/19880501
2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/26341740
Publication citations
-
Protocol
Goldschmidt H, Sonneveld P, Cremer FW, van der Holt B, Westveer P, Breitkreutz I, Benner A, Glasmacher A, Schmidt-Wolf IG, Martin H, Hoelzer D, Ho AD, Lokhorst HM, , , Joint HOVON-50/GMMG-HD3 randomized trial on the effect of thalidomide as part of a high-dose therapy regimen and as maintenance treatment for newly diagnosed myeloma patients., Ann. Hematol., 2003, 82, 10, 654-659, doi: 10.1007/s00277-003-0685-2.
-
Results
Breitkreutz I, Lokhorst HM, Raab MS, Holt Bv, Cremer FW, Herrmann D, Glasmacher A, Schmidt-Wolf IG, Blau IW, Martin H, Salwender H, Haenel A, Sonneveld P, Goldschmidt H, Thalidomide in newly diagnosed multiple myeloma: influence of thalidomide treatment on peripheral blood stem cell collection yield., Leukemia, 2007, 21, 6, 1294-1299, doi: 10.1038/sj.leu.2404661.
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Results
Lokhorst HM, van der Holt B, Zweegman S, Vellenga E, Croockewit S, van Oers MH, von dem Borne P, Wijermans P, Schaafsma R, de Weerdt O, Wittebol S, Delforge M, Berenschot H, Bos GM, Jie KS, Sinnige H, van Marwijk-Kooy M, Joosten P, Minnema MC, van Ammerlaan R, Sonneveld P, , A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma., Blood, 2010, 115, 6, 1113-1120, doi: 10.1182/blood-2009-05-222539.
-
Results
Lokhorst HM, van der Holt B, Zweegman S, Vellenga E, Croockewit S, van Oers MH, von dem Borne P, Wijermans P, Schaafsma R, de Weerdt O, Wittebol S, Delforge M, Berenschot H, Bos GM, Jie KS, Sinnige H, van Marwijk-Kooy M, Joosten P, Minnema MC, van Ammerlaan R, Sonneveld P, , A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma., Blood, 2010, 115, 6, 1113-1120, doi: 10.1182/blood-2009-05-222539.