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| [ Print-friendly version ] |
| 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 |
| ClinicalTrials.gov identifier | |
| Public title | 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 |
| Scientific title | |
| Acronym | HOVON65/GMMG-HD4 |
| Serial number at source | 26866138MMY3003; HO65 |
| Study hypothesis | 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. |
| Lay summary | Not provided at time of registration |
| Ethics approval | Ethics approval received from the local medical ethics committee |
| Study design | Prospective, multicentre, randomised, active controlled, parallel group trial |
| Countries of recruitment | Germany |
| Disease/condition/study domain | Multiple myeloma |
| Participants - 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 |
| Participants - 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 |
| Anticipated start date | 01/05/2005 |
| Anticipated end date | 30/09/2011 |
| Status of trial | Completed |
| Patient information material | |
| Target number of participants | 800 |
| Interventions |
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. |
| Primary outcome measure(s) | Progression Free Survival (PFS), i.e. time from registration to progression, relapse or death from any cause. |
| Secondary outcome measure(s) |
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. |
| Sources of funding |
1. Johnson & Johnson
2. Amgen 3. Chugai 4. Novartis 5. Roche 6. German Federal Ministry of Education and Research |
| Trial website | http://www.hovon.nl |
| Publications |
1. 2011 results in http://www.ncbi.nlm.nih.gov/pubmed/21791469
2. 2011 results in http://www.ncbi.nlm.nih.gov/pubmed/22160383 |
| Contact name | Prof Pieter Sonneveld |
| Address |
Erasmus MC
Dept of Hematology P.O. Box 2040 |
| City/town | Rotterdam |
| Zip/Postcode | 3000 CA |
| Country | Netherlands |
| p.sonneveld@erasmusmc.nl | |
| Sponsor | Dutch Haemato-oncology Association (Stichting Haemato-Oncologie voor Volwassenen Nederland [HOVON]) |
| Address |
VU Medisch Centrum
P.O. Box 7057 |
| City/town | Amsterdam |
| Zip/Postcode | 1007 MB |
| Country | Netherlands |
| f.barbieri@vumc.nl | |
| Date applied | 13/09/2005 |
| Last edited | 20/12/2011 |
| Date ISRCTN assigned | 03/11/2005 |
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| © 2012 ISRCTN unless otherwise stated. | |
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