To assess the feasibility, defined as discontinuation rate, of a dose-adapted MPV scheme in MM patients >= 75 years
ID
Source
Brief title
Condition
- Plasma cell neoplasms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Discontinuation rate, defined as the proportion of patients who received less
than 9 cycles of MPV according to protocol treatment
Secondary outcome
- Relative dose intensity of Melphalan, Prednisone and Bortezomib
- Safety and toxicity as defined by type, frequency and severity of adverse
events as defined by the National Cancer Institute (NCI) Common Terminology
Criteria (CTC), version 4.0
- Overall response rate defined as sCR, CR, VGPR or PR
- Progression free survival, defined as time from registration to progression
or death from any cause
- Overall survival, measured from time of registration
- Geriatric assessments
- Quality of life as defined by the EORTC QLQ-C30 and MY-20 definitions.
- Biomarkers for biological age
- Genetic polymorphism analysis of genes involved in drug metabolism and
related with bortezomib-induced PNP
- Cost efficacy analysis
Background summary
The prognosis of MM patients has increased significantly over the last decade
with the availability of new drugs. This also accounts for the elderly patients
with MM >65 years of age. However, toxicity of the treatment leading to
discontinuation of therapy and an inferior outcome remains a concern.
Especially in those patients over 75 years of age, because of vulnerability due
to co-morbidities complicating the treatment of MM. Appropriate screening for
vulnerability and an assessment of cardiac, pulmonary, renal, hepatic and
neurologic functions at the start of therapy allows treatment strategies to be
individualized an drug doses to be tailored to improve tolerability and
optimize efficacy. However, there is a lack of information on geriatric
assessments predicting the feasibility of MM treatment and the need for dose
reductions preferably without hampering outcome in MM patients. Only recently a
high risk vulnerability score based on PS and CCI was found to be associated
with outcome in a retrospective analysis of a non-uniformly described group of
MM patients. Therefore, currently applied treatment algorithms in the elderly
are based on age (< versus >=75 years of age) and co-morbidities, not being
precisely defined, are mainly based on expert opinions instead of based on
clinical outcome. Adding the fact that geriatric assessments have currently not
been implemented, current clinical practice is characterized by *individual
physician impression-based dose adjustments*. As a consequence either
irreversible toxicity as well as unnecessary loss of efficacy will occur,
hampering QoL, duration of life and cost efficacy.
This study aims to assess the feasibility of a well defined dose-adjusted MPV
scheme in patients >=75 years of age and to assess the additive value of
geriatric assessments to predict both feasibility and efficacy. In addition,
the value of new biomarkers reflecting biological age will be investigated.
Finally, a QoL and cost-efficacy analysis will be performed. This will
hopefully lead to a geriatric assessment-based treatment in MM patients in the
near future.
Study objective
To assess the feasibility, defined as discontinuation rate, of a dose-adapted
MPV scheme in MM patients >= 75 years
Study design
multi center phase 2 study
Intervention
The patients will be treated with the standard therapy for this patient
population.
Study burden and risks
The specific side effects of the medication, participation in the geriatric
assessment taking time of patients and a minor invasive skin biopsy will be
performed.
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
- Previously untreated patients with a confirmed diagnosis of symptomatic multiple myeloma according to IMWG criteria
- Age >= 75 years
- WHO performance status 0-3, WHO 4 performance status is allowed when related to MM
- Measurable disease as defined by the presence of M-protein in serum or urine and/or abnormal free light chain (FLC) ratio with involved FLC. (If plasmacytoma is the only measurable parameter, the patient is not allowed to be included in the study, because of difficult response evaluation)
- Patient gives consent for extra bone marrow, blood and skin biopsy sampling
- Written informed consent
Exclusion criteria
- Non-secretory MM
- Systemic Amyloid Light-chain amyloidosis
- Polyneuropathy, grade 1 with pain or >= grade 2
- Severe cardiac dysfunction (NYHA classification IV)
- Severe pulmonary dysfunction defined as breathlessness at rest
- Significant hepatic dysfunction (total bilirubin >= 30 µmol/l or transaminases >= 3 times normal level), unless related to MM
- Renal insufficiency requiring dialysis
- Patients with active, uncontrolled infections
- Pre-treatment with cytostatic drug, IMIDs or proteasome inhibitors. Radiotherapy or a short course of steroids (e.g. 4 day treatment of dexamethasone 40 mg/day or equivalent) are allowed.
- Patients known to be HIV-positive
- Active malignancy requiring treatment or having been treated with chemotherapy currently affecting bone marrow capacity. Non-active previous malignancies are allowed.
- Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule
- Patients with plasma cell leukemia
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 | EUCTR201300032033-NL |
| CCMO | NL43698.029.13 |