Multiple Myeloma MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Sponsors
HOVON Foundation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patients with a confirmed diagnosis of symptomatic multiple myeloma stage I to III according to the International Staging System ISS (see appendix A), i.e. at least one of the CRAB criteria should be present; -Measurable disease as defined by the presence of M-protein in serum or urine (serum M-proteïn > 10 g/l or urine M-proteïn > 200 mg/24 hours) or abnormal free light chain ratio with involved free light chain (FLC) > 100 mg/l or proven plasmacytoma by biopsy - Age 18-65 years inclusive; - WHO performance status 0-3 (WHO=3 is allowed only when caused by MM and not by co-morbid conditions) - Negative pregnancy test at inclusion if applicable; - Written informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 1500 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Known intolerance of Boron; - Systemic AL amyloidosis; - Primary Plasmacell Leukemia; - Non-secretory MM; - Previous chemotherapy or radiotherapy except local radiotherapy in case of local myeloma progression or corticosteroids maximum 5 days for symptom control; - Severe cardiac dysfunction (NYHA classification II-IV, see appendix E); - Significant hepatic dysfunction (serum bilirubin >= 30 mmol/l or transaminases >= 2.5 times normal level), unless related to myeloma; - Patients with GFR <15 ml/min, - Patients known to be HIV-positive; - Patients with active, uncontrolled infections; - Patients with neuropathy, CTC grade 2 or higher; - 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; - Patients who are not willing or capable to use adequate contraception during the therapy (all men, all pre-menopausal women); -Lactating women;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To assess the efficacy of VMP versus high-dose therapy and stem cell transplantation (HDT) in patients with previously untreated multiple myeloma, as measured by the progression free survival. - To evaluate the effect of consolidation with VRD followed by Lenalidomide maintenance with no consolidation but Lenalidomide maintenance alone on progression free survival. ;Secondary Objective: -To compare VMP versus single HDT+ ASCT; or VMP versus tandem HDT + ASCT; or single versus tandem HDT + ASCT. -To compare overall response rate and CR + VGPR (complete and very good partial response) after induction therapy, after VMP or HDT, after consolidation and during maintenance. -To evaluate overall survival. -To assess safety and toxicity -To assess the prognostic value of risk factors at diagnosis, including b2-microglobulin, FISH abnormalities del1p, ampli 1q, t(4;14), t(14;16), t(11;14), ampli 9, del13q/13-, del17p as analyzed in purified bone marrow plasma cells with respect to progression free survival. -To analyze the prognostic value of myeloma gene expression profiles on the overall response on induction of all patients and of patients treated in the different randomization arms. - To assess quality of life;Primary end point(s): - For all registered patients: progression free survival (PFS) as defined by time from registration to progression or death from any cause whichever occurs first). -F or all patients included in R1; PFS as defined by time from randomization R1 to progression or death from any cause whichever comes first - For all patients included in R2; PFS as defined by time from randomization R2 to progression or death from any cause whichever comes first ;Timepoint(s) of evaluation of this end point: Two interim analyses are planned for each randomization, primarily to guard against unfavorable results in the HDM and in the VRD consolidation arms. Results of the interim analyses will be presented confidentially to an independent data a | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Response (PR, VGPR, CR and stringent CR), and improvement of response during the various stages of the treatment. - Overall survival measured from the time of registration/randomization R1/ randomization R2. Patients still alive or lost to follow up are censored at the date they were last known to be alive. - Toxicity. - Quality of life as defined by the EORTC QLQ-C30 and QLQ-MY20 definitions.;Timepoint(s) of evaluation of this end point: Two interim analyses are planned for each randomization, primarily to guard against unfavorable results in the HDM and in the VRD consolidation arms. Results of the interim analyses will be presented confidentially to an independent data and safety monitoring board (DSMB). Only if the DSMB recommends that the study should be stopped or modified the results will be made public to the principal investigators for further decisions. The interim analyses are planned after 33% and 66% of the events with regard to PFS from R1 and R2 have been observed (240/480 resp. 172/343), which are the primary endpoints for these analyses. | — |
Countries
Australia, Austria, Belgium, Croatia, Czechia, Czech Republic, Denmark, Estonia, Finland, Germany, Greece, Hungary, Iceland, Ireland, Israel, Italy, Luxembourg, Netherlands, Norway, Poland, Portugal, Serbia, Slovakia, Slovenia, Sweden, Switzerland, Turkey
Contacts
Public ContactHOVON Data Center
HOVON
Outcome results
None listed