To compare efficacy, safety and quality of life of MP-Thal followed by thalidomide maintenance versus MP-Len followed by maintenance with lenalidomide
ID
Source
Brief title
Condition
- Plasma cell neoplasms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Progression free survival, defined as time from registration to progression
or death from any cause
- Response rate (sCR, CR or VGPR)
Secondary outcome
- Response rate (sCR, CR, VGPR or PR)
- Overall survival, measured from time of registration
- Quality of response during maintenance, measured as improvement of response
(from start maintenance till progression)
- Time to maximum response, defined as time from registration to maximum
response
- 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 3.0
- Quality of life.
Background summary
Until recently melphalan/prednisone (MP) has been the standard combination of
drug treatment for patients with Multiple Myeloma (MM) at an elderly age. With
MP the response rate is approximately 50%, of which < 5 % are complete
responses (CR). Addition of thalidomide to MP (MP-Thal) increases the overall
response (OR), complete response (CR) and event-free survival (EFS) as
demonstrated in two recent randomized trials. Moreover, a significant increase
in survival has recently be found: 51.5 months in MPT treated patients versus
33.2 months in MP treated patients.However, despite these improvements, the
majority of patients develop a relapse or progressive disease in relatively
short time, as indicated by an EFS of 54% at two years in patients treated with
MP-Thal. Therefore, there is a need to further explore the role of novel
agents, such as Lenalidomide in the upfront treatment of MM. Lenalidomide has
now been tested as single agent in MM, with clear clinical effects giving
response in 25% of patients in heavily pretreated patients, including
pretreatment with thalidomide. Responses up to 60% have been described in
combination with dexamethasone or bortezomib in pretreated patients. In
previously untreated patients, the combination of lenalidomide with MP was
found to be feasible in an elderly population and resulted in response in all
patients. Moreover, in contrast to thalidomide, lenalidomide has a safety
profile which does not include central or peripheral neuropathy. However,
hematological toxicity was found to be more frequent. As currently no data from
randomized studies comparing MP-Thal versus MP-Lenalidomide are available,
HOVON decided to initiate a Phase III randomized trial comparing MP-Thal versus
MP-Len. In both treatment arms maintenance therapy will be given, either
thalidomide or lenalidomide. Efficacy, toxicity and quality of life will be
compared.
Study objective
To compare efficacy, safety and quality of life of MP-Thal followed by
thalidomide maintenance versus MP-Len followed by maintenance with lenalidomide
Study design
Multicenter, randomized, phase III.
Intervention
Patients will be randomized between treatment with 9 cycles of MP-Thalidomide
followed bij Thalidomide maintenance until relapse/progression or treatment
with 9 cycles of MP-Lenalidomide followed by Lenalidomide maintenance until
relapse/progression
Study burden and risks
Toxicity, especially myelosuppression, polyneuropathy
De Boelelaan 1117
Amsterdam 1081 HV
NL
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 > 65 years or patients *
65 not eligible for high dose chemotherapy and peripheral stem cell
transplantation, - WHO performance status 0-3 for patients <75 years and WHO
performance status 0-2 for patients *75 years , - Measurable disease as defined
by the presence of M-protein in serum or urine or proven plasmocytoma by
biopsy, - Written informed consent
Exclusion criteria
- Non-secretory MM, - Known hypersensitivity to thalidomide, - Systemic AL
amyloidosis , - Polyneuropathy, grade 2 or higher , - Severe cardiac
dysfunction (NYHA classification II-IV) , - Severe pulmonary dysfunction , -
Significant hepatic dysfunction (total bilirubin *30 umol/l or transaminases *3
times normal level), unless related to myeloma , - Creatinine clearance < 30
ml/min, - 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 , - History of active malignancy
during the past 5 years, except basal carcinoma of the skin or stage 0 cervical
carcinoma , - Not able and/or not willing to use adequate contraception , -
Pregnancy
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 | EUCTR2007-004007-34-NL |
| CCMO | NL24321.029.08 |