7 maart 2013

Originele protocol

Behandelschema patiënt

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 Mprotein > 10 g/l or urine M-protein > 200 mg/24 hours or abnormal FLC ratio with involved free light chain (FLC) > 100 mg/l) or proven plasmacytoma by biopsy;), 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) (see appendix D);
  • Negative pregnancy test at inclusion if applicable;
  • Written informed consent.

Randomization 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 10^6 CD34+ cells/kg (or according to national guidelines).

Randomization 2

  • Bilirubin and transaminases < 2.5 times the upper limit of normal values;
  • ANC >= 0.5 x 10^9/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, 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.

Randomization 1

  • Severe pulmonary, neurologic, or psychiatric disease;
  • CTCAE grade 3-4 polyneuropathy during Bortezomib treatment;
  • Allogeneic Stem Cell Transplantation (Allo SCT) planned;
  • Progressive disease.

Randomization 2

  • Progressive disease;
  • Neuropathy, except CTCAE grade 1;
  • CTCAE grade 3-4 polyneuropathy during Bortezomib treatment.