A randomised phase III study on the effect of bortezomib combined with adriamycin, dexamethasone (AD) for induction treatment, followed by high dose melphalan and bortezomib alone during maintenance in patients with multiple myeloma
| ISRCTN | ISRCTN64455289 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN64455289 |
| EudraCT/CTIS number | 2004-000944-26 |
| Secondary identifying numbers | 26866138MMY3003; HO65 |
- Submission date
- 13/09/2005
- Registration date
- 03/11/2005
- Last edited
- 03/09/2013
- 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 Pieter Sonneveld
Scientific
Scientific
Erasmus MC
Dept of Hematology
P.O. Box 2040
Rotterdam
3000 CA
Netherlands
| p.sonneveld@erasmusmc.nl |
Study information
| Study design | Prospective, multicentre, randomised, active controlled, parallel group trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Not specified |
| Study type | Treatment |
| Scientific title | |
| Study acronym | HOVON65/GMMG-HD4 |
| Study objectives | Bortezomib combined with intensive chemotherapy and in maintenance therapy is superior in comparison with intensive therapy with vincristine followed by thalidomide maintenance in patients with previously untreated multiple myeloma, as measured by response rate and progression-free and overall survival. |
| Ethics approval(s) | Ethics approval received from the local medical ethics committee |
| Health condition(s) or problem(s) studied | Multiple myeloma |
| Intervention | Arm A: Standard Vincristine, Adriamycin and Dexamethasone (VAD) induction, followed by intensive chemotherapy with melphalan 200 mg/m^2 and autologous blood stem cell transplantation, followed by maintenance therapy with thalidomide. Arm B: Induction chemotherapy with Bortezomib, Adriamycin and Dexamethasone (BAD) followed by intensive chemotherapy with melphalan 200 mg/m^2 and autologous blood stem cell transplantation, followed by maintenance with bortezomib. Duration of treatment: Expected duration of induction, stem cell collection and intensification (with or without Bortezomib) is six to seven months. Maintenance therapy with Bortezomib or Thalidomide will be given for two years. Please note that the anticipated end date of this trial has been shortened to 22nd April 2007. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Bortezomib, vincristine, adriamycin, dexamethasone and melphalan |
| Primary outcome measure | Progression Free Survival (PFS), i.e. time from registration to progression, relapse or death from any cause. |
| Secondary outcome measures | 1. Response (Partial Remission [PR], very Good Partial Remission [vGPR] and Complete Remission [CR]) 2. Overall Survival (OS) 3. PFS from High-Dose Therapy (HDT) i.e. time from last High-Dose Melphalan (HDM) treatment to progression, relapse or death from any cause whichever occurs first for patients who received at least PR on HDT 4. Toxicity 5. PFS analysed as primary endpoint, but patients with an allogeneic transplant not censored. This primarily to check whether censoring has a major impact. |
| Overall study start date | 01/05/2005 |
| Completion date | 30/09/2011 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 800 |
| Key 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 (WHO = three is allowed only when caused by multiple myeloma and not by co-morbid conditions) 4. Negative pregnancy test at inclusion if applicable 5. Written informed consent |
| Key exclusion criteria | 1. Known intolerance of thalidomide or boron 2. Systemic AL amyloidosis 3. Non-secretory multiple myeloma 4. Previous chemotherapy or radiotherapy except two cycles of melphalan/prednisone or local radiotherapy in case of local myeloma progression 5. Severe cardiac dysfunction (New York Heart Association [NYHA] classification II - IV) 6. Significant hepatic dysfunction (serum bilirubin more than or equal to 30 µmol/l or transaminases more than or equal to 2.5 times normal level), unless related to myeloma 7. Patients known to be Human Immunodeficiency Virus (HIV) positive 8. Patients with active, uncontrolled infections 9. Patients with neuropathy, CTC grade two or higher 10. Patients with a history of active malignancy during the past five years with the exception of basal carcinoma of the skin or stage zero cervical carcinoma 11. Patients who will not give permission for collection of Bone Marrow (BM) aspirate at entry 12. Patients who are not willing or capable to use adequate contraception during the therapy (all men, all pre-menopausal women) 13. Patients 65 years or less with a Human Leukocyte Antigen (HLA) identical sibling who will undergo non-myeloablative AlloSCT 14. Lactating women |
| Date of first enrolment | 01/05/2005 |
| Date of final enrolment | 30/09/2011 |
Locations
Countries of recruitment
- Germany
- Netherlands
Study participating centre
Erasmus MC
Rotterdam
3000 CA
Netherlands
3000 CA
Netherlands
Sponsor information
Dutch Haemato-oncology Association (Stichting Haemato-Oncologie voor Volwassenen Nederland [HOVON])
Research organisation
Research organisation
VU Medisch Centrum
P.O. Box 7057
Amsterdam
1007 MB
Netherlands
| f.barbieri@vumc.nl | |
"ROR" |
https://ror.org/056kpdx27 |
Funders
Funder type
Industry
Johnson & Johnson
Government organisation / For-profit companies (industry)
Government organisation / For-profit companies (industry)
- Alternative name(s)
- Johnson & Johnson, johnson & Johnson Services, Inc., Johnson&Johnson, 强生公司, Johnson & Johnson Private Limited, ジョンソン・エンド・ジョンソント, J&J, JNJ
- Location
- United States of America
Amgen
Government organisation / For-profit companies (industry)
Government organisation / For-profit companies (industry)
- Alternative name(s)
- Amgen Inc., Applied Molecular Genetics Inc.
- Location
- United States of America
Chugai
No information available
Novartis
Government organisation / For-profit companies (industry)
Government organisation / For-profit companies (industry)
- Alternative name(s)
- Novartis AG, Novartis International AG
- Location
- Switzerland
Roche
Government organisation / For-profit companies (industry)
Government organisation / For-profit companies (industry)
- Alternative name(s)
- F. Hoffmann-La Roche Ltd, F. Hoffmann-La Roche & Co, F. Hoffmann-La Roche AG, Roche Holding AG, Roche Holding Ltd, Roche Holding, Roche Holding A.G., Roche Holding, Limited, F. Hoffmann-La Roche & Co.
- Location
- Switzerland
German Federal Ministry of Education and Research
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| 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? |
|---|---|---|---|---|---|
| Results article | results | 01/11/2011 | Yes | No | |
| Results article | results | 26/01/2012 | Yes | No | |
| Results article | results | 24/01/2013 | Yes | No | |
| Results article | results | 01/01/2014 | Yes | No |
