The aim of this study is to improve the outcome of both younger and elderly primary plasma cell leukemia patients(pPCL) by using next generation novel agents and in case of younger patients also the tandem of auto-SCT and allo-SCT.
ID
Source
Brief title
Condition
- Plasma cell neoplasms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Progression-free survival (PFS, i.e. time from registration until progression
or death, whichever comes first)
Secondary outcome
- Safety and toxicity as defined by type, frequency and severity of adverse
events as defined by the National Cancer Institute (NCI) Common Terminology
Criteria for Adverse Events (CTCAE), version 4
- 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, 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
Background summary
Primary plasma cell leukemia (pPCL) is the most aggressive form of the plasma
cell dyscrasias. It is defined by the presence of >2x109/L peripheral blood
plasma cells or plasmacytosis accounting for >20% of the differential white
cell count, and does not arise from pre-existing multiple myeloma (MM.
The prognosis of pPCL is very poor, with a median overall survival (OS) of only
7 months with standard chemotherapy. The introduction of autologous stem cell
transplantation (auto-SCT) and the novel agents, especially bortezomib, has
recently improved outcome of patients with pPCL, but remains inferior when
compared to MM. Therefore innovative treatment approaches which incorporate
various modalities are required to improve outcome.
Lenalidomide with carfilzomib and dexamethasone (CRd) is a regimen that
combines high efficacy with low rate of polyneuropathy and is therefore an
attractive combination for induction treatment in pPCL.
Furthermore, allogeneic stem cell transplantation (allo-SCT) is a form of
consolidation treatment, which by virtue of the graft-versus-tumor effect,
results in a high rate of molecular remissions in plasma cell cancers. Several
small studies reported successful results and long-term survival following
allo-SCT in pPCL
.
In this study, the CRd regimen will be used as induction therapy. In case of
younger transplant-eliglible patients (18-65 years), CRd will also be used as
consolidation and maintenance treatment after high-dose therapy with autologous
stem cell rescue and allogeneic stem cell transplantation. Elderly patients
(>=66 years) with pPCL will receive carfilzomib and lenalidomide maintenance
after induction therapy.
Study objective
The aim of this study is to improve the outcome of both younger and elderly
primary plasma cell leukemia patients(pPCL) by using next generation novel
agents and in case of younger patients also the tandem of auto-SCT and
allo-SCT.
Study design
Multicenter, intergroup, phase 2 study
Intervention
Patients will be treated with a combinatin of carfilzomib, lenalidomide and
dexamethasone (CRd) followed by auto-stem cell transplantation and
consolidation with CRd, or if possible an allo stem cell transplantation with
CR in maintenance until progression.
Study burden and risks
Patients will be treated with a highly effective combination of drugs during
induction, consolidation, and maintenance phases. Toxicity will be mainly
hematologic.
HOVON Centraal Bureau, VUMC, De Boelelaan 1117
Amsterdam 1081 HV
NL
HOVON Centraal Bureau, VUMC, De Boelelaan 1117
Amsterdam 1081 HV
NL
Listed location countries
Age
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 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, and 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 or to any of the excipients of the
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 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
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-005157-75-NL |
| CCMO | NL47727.029.14 |