Primary plasma cell leukemia MedDRA version: 20.0 Level: LLT Classification code 10035223 Term: Plasma cell leukemia System Organ Class: 100000004864
Conditions
Interventions
Product Name: Carfilzomib
Product Code: L01XX45
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Carfilzomib
CAS Number: 868540-17-4
Current Sponsor code: NA
Concentration unit: mg/ml m
Sponsors
HOVON
Eligibility
Sex/Gender
All
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 > 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) Are the trial subjects under 18? no Number of subjects for this age range: 1 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 61 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 55
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 |
|---|---|
| Main Objective: To evaluate progression-free survival in adult pPCL patients by incorporation of carfilzomib and lenalidomide in induction, consolidation, and maintenance therapy;Secondary Objective: - To assess overall response rate and (s)CR + VGPR ((stringent) complete and very good partial response) rate after induction therapy, after HDM, after CRd consolidation, after RIC allo-SCT or a second HDM, and during maintenance. - To evaluate overall survival. - To assess safety and toxicity - To assess the prognostic value of risk factors at diagnosis, including ß2-microglobulin, LDH, FISH abnormalities del1p, ampli 1q, t(4;14), t(14;16), t(11;14), ampli 9, del13q/13-, del17p as analyzed in purified bone marrow plasma cells with respect to progression-free survival - To analyze the prognostic value of myeloma gene expression profiles - To analyze the prognostic value of minimal-residual disease negativity - To assess the prognostic value of mutations as determined by sequencing - To analyze the prognostic value of minimal-residual disease negativity - To establish the frequency of second primary malignancies (SPM);Primary end point(s): Progression-free survival (PFS, i.e. time from registration until progression or death, whichever comes first).;Timepoint(s) of evaluation of this end point: At the end of the trial. After last patient has completed maintenance treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - 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 including FISH abnormalities, ß2-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;Timepoint(s) of evaluation of this end point: At the end of the trial. After last patient has completed maintenance treatment. | — |
Countries
Belgium, Denmark, Germany, Italy, Netherlands, Norway, Sweden
Contacts
Public ContactHOVON Data Center
HOVON
Outcome results
None listed