HOVON 129

Originele protocol

Carfilzomib and lenalidomide-based treatment for younger and elderly newly diagnosed primary plasma cell leukemia patients
A European Intergroup Trial of the European Myeloma Network EMN (EMN12/HO129 PCL)

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Inclusion criteria

  • Patients with diagnosis of symptomatic pPCL (see appendix A)
  • 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 FLC ratio with involved free light chain (FLC) > 100 mg/l) or proven plasmacytoma by biopsy)
  • Age ≥18 years
  • WHO-performance status 0-3 (but WHO=3 is allowed only when caused by pPCL and not by co-morbid conditions)
  • Written informed consent
  • Patient capable of giving informed consent (patient is legally, physically and mentally capable of giving consent)
  • All men and women of childbearing potential should use adequate contraception during the study. Sperm could be frozen from men with child wish before start of treatment
  • Negative pregnancy test at entry (if applicable)
  • Patient is willing and able to adhere to the requirements of the lenalidomide Pregnancy Prevention Program (PPP)

Exclusion criteria

  • Any current CNS involvement with disease refractory to intrathecal chemotherapy.
  • Female patients who are pregnant or breast feeding.
  • HIV positive patients
  • Active malignancy other than pPCL requiring treatment, or a malignancy that has been treated with chemotherapy currently affecting bone marrow capacity
  • Patients with active, uncontrolled infections
  • Severe neurological or psychiatric disease
  • Severe cardiac dysfunction (NYHA classification II-IV, see appendix E)
  • Severe pulmonary dysfunction
  • Significant hepatic dysfunction (serum bilirubin or transaminases ≥ 3.0 times normal level), unless related to pPCL
  • Patients with GFR < 15 ml/min
  • Known history of allergy to Capsidol (a cyclodextrin derivative used to solubilize carfilzomib)
  • Previous chemotherapy or radiotherapy except local radiotherapy in case of local myeloma progression or corticosteroids maximum 7 days for symptom control or stabilization(this includes dexamethasone 40 mg daily) or inthrathecal chemotherapy in case of CNS involvement
  • Systemic AL amyloidosis
  • Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule