Condition category
Cancer
Date applied
20/12/2005
Date assigned
20/12/2005
Last edited
03/10/2016
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

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

http://www.hovon.nl/

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

  1. 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.

  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.

  3. 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.

  4. 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.

Additional files

Editorial Notes

03/10/2016: Publication reference added.