|- candidate number||1377|
|- NTR Number||NTR213|
|- Date ISRCTN created||3-nov-2005|
|- date ISRCTN requested||18-okt-2005|
|- Date Registered NTR||5-sep-2005|
|- Secondary IDs||HO65 |
|- Public Title||A randomized 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||A randomized 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.|
|- ACRONYM||HOVON 65 MM / GMMG-HD4|
|- hypothesis||The hypothesis to be tested is that the outcome in arm B is better than in arm A.|
|- Healt Condition(s) or Problem(s) studied||Multiple myeloma (Kahler's disease)|
|- Inclusion criteria||1. Patients with a confirmed diagnosis of multiple myeloma stage II or III according to the Salmon & Durie criteria;|
2. Age 18-65 years inclusive;
3. WHO performance status 0-3 (WHO=3 is allowed only when caused by MM and not by co-morbid conditions);
4. Negative pregnancy test at inclusion if applicable;
5. Written informed consent.
|- Exclusion criteria||1. Known intolerance of Thalidomide or Boron;|
2. Systemic AL amyloidosis;
3. Non-secretory MM;
4. Previous chemotherapy or radiotherapy except 2 cycles of Melphalan/Prednisone or local radiotherapy in case of local myeloma progression;
5. Severe cardiac dysfunction (NYHA classification II-IV);
6. Significant hepatic dysfunction (serum bilirubin >= 30 mmol/l or transaminases >= 2.5 times normal level), unless related to myeloma;
7. Patients known to be HIV-positive;
8. Patients with active, uncontrolled infections;
9. Patients with neuropathy, CTC grade 2 or higher;
10. Patients with a history of active malignancy during the past 5 years with the exception of basal carcinoma of the skin or stage 0 cervical carcinoma;
11. Patients who will not give permission for collection of 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 with an HLA-identical sibling who will undergo non-myeloablative AlloSCT;
14. Lactating women.
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||22-apr-2005|
|- planned closingdate||22-apr-2007|
|- Target number of participants||800|
|- Interventions||Patients with multiple myeloma, meeting all eligibility criteria will be randomized on entry between:
Standard Vincristine, Adriamycin and Dexamethasone (VAD) induction, followed by intensive chemotherapy with High-dose Melphalan, followed by maintenance therapy with Thalidomide
induction chemotherapy with Bortezomib, Adriamycin and Dexamethasone (PAD) followed by intensive chemotherapy with High-dose Melphalan, followed by maintenance with Bortezomib.
|- Primary outcome||Progression free survival (i.e. time from registration to progression or death from any cause whichever occurs first).|
|- Secondary outcome||1. Response (PR, VGPR and CR);|
2. Overall survival measured from the time of registration. Patients still alive or lost to follow up are censored at the date they were last known to be alive;
4. Progression free survival from HDM (i.e. time from last HDM treatment to progression or death from any cause whichever occurs first for patients who received at least PR on HDM);
5. Progression free survival analysed as primary endpoint, but patients with an allogeneic transplant not censored. This primarily to check whether censoring has a major impact.
|- Trial web site||http://www.hovon.nl|
|- status||inclusion stopped: follow-up|
|- CONTACT FOR PUBLIC QUERIES||Prof. Dr. P. Sonneveld|
|- CONTACT for SCIENTIFIC QUERIES||Prof. Dr. P. Sonneveld|
|- Sponsor/Initiator ||Erasmus Medical Center, Daniel den Hoed Cancer Center , VU University Medical Center, Dutch haemato-oncology association (Stichting Hemato-Oncologie voor Volwassenen Nederland (HOVON)|
(Source(s) of Monetary or Material Support)
|Koningin Wilhelmina Fonds (KWF), Stichting Hemato-Oncologie voor Volwassenen Nederland (HOVON), Johnson & Johnson|
|- Brief summary||Study phase: |
Evaluation of the effect of Bortezomib in addition to AD and High Dose Melphalan for induction and maintenance treatment.
Patients with multiple myeloma, previously untreated, Salmon & Durie stage II or III, age 18-65 years inclusive.
Prospective, multicenter, randomized.
Duration of treatment:
Expected duration of induction, stem cell collection and intensification (with or without Bortezomib) is 6 -7 months. Maintenance therapy with Bortezomib or Thalidomide will be given for 2 years.
|- Main changes (audit trail)|
|- RECORD||5-sep-2005 - 27-nov-2009|