Newly diagnosed symptomatic Multiple Myeloma MedDRA version: 20.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Velcade
Pharmaceutical Form: Powder for solution for injection/infusion
INN or Proposed INN: BORTEZOMIB
CAS Number: 179324-69-7
Concentration unit: mg/m2 milligram(s)/square meter
Concentr
Sponsors
HOVON Foundation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Previously untreated patients with a confirmed diagnosis of symptomatic multiple myeloma according to IMWG criteria (see appendix A) - Age = 75 years - WHO performance status 0-3, WHO 4 performance status is allowed when related to MM (see appendix E) - Measurable disease as defined by the presence of M-protein in serum or urine or proven plasmacytoma by biopsy (see appendix A for definitions) (If plasmacytoma is the only measurable parameter, the patient is not allowed to be included in the study, because of difficult response evaluation). -Patient gives consent for extra bone marrow, blood and skin biopsy sampling. -Written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 240
Exclusion criteria
Exclusion criteria: - Non-secretory MM - Systemic Amyloid Light-chain (AL) amyloidosis - Polyneuropathy, grade 1 with pain or grade = 2 - Severe cardiac dysfunction (NYHA classification IV, appendix F) - Severe pulmonary dysfunction defined as breathlessness at rest - Significant hepatic dysfunction (total bilirubin = 30 µmol/l or transaminases = 3 times normal level), unless related to MM - Renal insufficiency requiring dialysis - Patients with active, uncontrolled infections - Pre-treatment with cytostatic drug, imunnomodulatory drugs (IMiDs) or proteasome inhibitors. Radiotherapy or a short course of steroids (e.g. 4 day treatment of dexamethasone 40 mg/day or equivalent) are allowed - Patients known to be Human Immunodeficiency Virus (HIV)-positive - Active malignancy other than MM requiring treatment or a malignancy that has been treated with chemotherapy currently affecting bone marrow capacity - Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule - Patients with plasma cell leukemia
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the feasibility, defined as discontinuation rate, of a dose-adapted MPV scheme in MM patients = 75 years of age;Secondary Objective: • To assess toxicity • To assess efficacy determined as response rate, PFS and OS • To assess time to response • To assess the relative dose intensity of MPV • To assess the cumulative dose intensity of MPV • To assess the predictive value of geriatric assessments, biomarkers reflecting biological age and sarcopenia with respect to feasibility and efficacy • To assess QoL • To analyze the value of polymorphism of genes involved in drug metabolism in predicting bortezomib-induced PNP • To assess the prognostic value of risk factors at diagnosis, including ß2-microglobulin and chromosomal abnormalities • To analyze the prognostic value of myeloma gene expression profiles • Cost effectiveness analysis ;Primary end point(s): Discontinuation rate, defined as the proportion of patients who received less than 9 cycles of MPV according to protocol treatment;Timepoint(s) of evaluation of this end point: Evaluation of this endpoint will take place as soon as the relevant data of all patients are available and validated. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Evaluation of this endpoint will take place as soon as the relevant data of all patients are available and validated.;Secondary end point(s): - Safety and toxicity as defined by type, frequency and severity of adverse events as defined by the National Cancer Institute (NCI) Common Terminology Criteria (CTC), version 4.0 - Overall response rate where response is defined as sCR, CR, VGPR or PR - Time to response - Progression free survival , defined as time from registration to progression, relapse or death from any cause whichever occurs first - Overall survival, measured from time of registration to death. Patients still alive or lost to follow up are censored at the date they were last known to be alive (date last contact) - Relative dose intensity and cumulative dose intensity of Melphalan, Prednisone and Bortezomib - Predictive value of geriatric assessments - Quality of life as defined by the EORTC QLQ-C30 and MY-20 definitions - Association of biomarkers for biological age with toxicity and feasibility of the treatment - Associations with toxicity and with feasibility of the treatment regimen of polymorphism of genes involved in drug metabolism and related with bortezomib-induced PNP - Association of risk factors and myeloma gene expression profiles with prognosis - Cost effectiveness as defined by the EQ-5D and the involved costs | — |
Countries
Netherlands
Contacts
Public ContactHDC
HOVON Data Center
Outcome results
None listed