Multiple myeloma (Kahler's disease)
Conditions
Interventions
Patients with age 18-65 years will receive 4 cycles of CRd followed by HDM and auto-SCT, then consolidation therapy with 2 cycles of CRd, and subsequently if eligible and a suitable donor is available
66 years will receive 8 cycles of CRd followed by carfilzomib-lenalidomide maintenance until progression.
Sponsors
Stichting Hemato-Oncologie voor Volwassenen Nederland (HOVON)
Eligibility
Inclusion criteria
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 > 5 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
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| • Progression-free survival (PFS, i.e. time from registration until progression or death, whichever comes first) | — |
Secondary
| Measure | Time frame |
|---|---|
| • Overall response rate (at least PR) after the different phases of treatment • (s)CR + VGPR ((stringent) complete and very good partial response) after the different phases of treatment • Overall survival, defined as time from registration until death from any cause. Patients still alive at the date of last contact, will be censored • Toxicity and tolerability of the different phases of treatment • Explore the value of prognostic factors including FISH abnormalities, β2-microgloublin, LDH, MRD-negativity, pPCL gene expression profiles and sequencing results on the overall response, overall survival and progression–free survival • Frequency of second primary malignancies | — |
Contacts
Public ContactN.W.C.J. van de Donk
VUmc
Outcome results
None listed