study to compare vmp with hdm followed by vrd consolidation and lenalidomide maintenance in patients with newly diagnosed multiple myeloma

Conditions: Multiple Myeloma

Summary: study phase: phase iii study objective: * comparison of bortezomib, melphalan, prednisone (vmp) with high dose melphalan followed autologous stem cell transplantation (asct) * comparison of bortezomib, lenalidomide, dexamethasone(vrd) as consolidation versus no consolidation * comparison of single versus tandem high dose melphalan with asct patient population: patients with symptomatic multiple myeloma,previously untreated, iss stages 1-3, age 18-65 years inclusive study design: prospective, multicenter, intergroup, randomized duration of treatment: expected duration of induction, stem cell collection and intensification is 6 - 9 months. consolidation with vrd will last 2 months maintenance therapy with lenalidomide will be given until relapse. all patients will be followed until 10 years after registration.


Eligibility 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-protein\> 10 g/l or urine m-protein \> 200 mg/24 hours), or abnormal free light chain ratio; * age 18-65 years inclusive; * who performance status 0-3 (who=3 is allowed only when caused by mm and not by comorbid conditions); * negative pregnancy test at inclusion if applicable; * written informed consent. inclusion for randomisation 1: * who performance 0-2; * bilirubin and transaminases \< 2.5 times the upper limit of normal values; * a suitable stem cell graft containing at least 4 x 106 cd34+ cells/kg (or according to national guidelines). inclusion for randomisation 2: * bilirubin and transaminases \< 2.5 times the upper limit of normal values; * anc \>= 0.5 x 109/l and platelets \> 20 x 10\^9/l; * patient is able to adhere to the requirements of the lenalidomide pregnancy prevention risk management plan. 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); * significant hepatic dysfunction, 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. exclusion for randomisation 1: * severe pulmonary, neurologic, or psychiatric disease; * ctcae grade 3-4 polyneuropathy during bortezomib treatment; * allogeneic stem cell transplantation (allo sct) planned; * progressive disease.' exclusion for randomisation 2: * progressive disease; * neuropathy, except ctcae grade 1; * ctcae grade 3-4 polyneuropathy during bortezomib treatment.

Keywords: multiple myeloma (kahler's disease)