Main info

Identificatie:

HO129 PCL

Sponsor:

HOVON

Working group party:

Myeloma

Age:

>= 18

Stadium:

1st lijn

Echelon:

Level A

Included patients:

61

(of 61)

Active sites:

16

(of 28)

9 sites are pending

Title:

Carfilzomib and lenalidomide-based treatment for younger and elderly newly diagnosed primary plasma cell leukemia patients.

Timeline

News

Flow

Details

Phase:

Prospective Phase II study

Monitoring Type:

Not any more

Objectives:

Primary Objective

• To evaluate progression-free survival in adult pPCL patients by incorporation of carfilzomib and lenalidomide in induction, consolidation, and maintenance therapy

Secondary objectives

• 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 β2-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 establish the frequency of second primary malignancies

Eligibility

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 Mprotein > 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 highly effective contraception during the study. Men should be offered sperm banking before starting treatment (if applicable).
• Negative pregnancy test at entry (if applicable)
• Patient is willing and able to adhere to the requirements of the lenalidomide Pregnancy Prevention Program (PPP) throughout study treatment

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)
  • Myocardial infarction within 6 months
  • unstable angina
  • cardiac arrhythmias which are not controlled by conventional treatment (including medications and cardiac devices)
• 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)
• Hypersensitivity to the active substances (carfilzomib, lenalidomide, and dexamethasone) or to any of the excipients of these drug products
• 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 intrathecal 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

Registration Details

Participating Sites

= Active hospitals

= Inactive hospitals