Clinical trial NCT00602511: Thalidomide Versus Bortezomib in Melphalan Refractory Myeloma
Official title: Thalidomide Versus Bortezomib in Melphalan Refractory Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Myeloma
Keywords: Melfalan refractory multiple myeloma
Multiple myeloma
Relapsing
Refractory
Thalidomide
Bortezomib
Randomized clinical trial
Lead sponsor: Nordic Myeloma Study Group
Sponsor class: OTHER
First posted: 2008-01-28
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to compare thalidomide + dexamethasone with bortezomib + dexamethasone in patients with multiple myeloma refractory to melphalan therapy. The main goal is to find out which of these two 2:nd line regimens that offers the patients the best chance for a response with as long duration and as good quality of life as possible.

Detailed description: The study is an open randomized multicentre study in which patients with multiple myeloma refractory to melphalan therapy are randomized between bortezomib and thalidomide therapy, in both arms with the addition of dexamethasone. In case of failure to the initially given treatment the patient will be crossed over to the alternative treatment.

The number of patients needed is calculated to 300, based upon the hypothesis of a 50% difference in progression free survival, a significance level of 95% and a power of 80%. With 12 patients being recruited each month during 25 months and a 4 months follow-up after the last included patient, the total study time will be 29 months.

The dose regimens for bortezomib and thalidomide follow general clinical praxis as regards recommendations for optimal dosing in the Nordic countries.

Evaluation of response and toxicity is performed every 3 weeks for at least 12 weeks, thereafter every 6 weeks. Evaluation of efficacy is done according to The International Myeloma Working Group Uniform Response Criteria. Evaluation of toxicity is done by CTCAE grading. Evaluation of quality of life is done by the EORTC QLQ30 questionnaires with the addition of the myeloma specific MY-24 module which are mailed to the patients at predetermined intervals during the study.

Eligibility criteria: Inclusion Criteria:

* Treatment demanding multiple myeloma
* Refractoriness to melphalan
* Acceptance of rules for prevention of pregnancy

Exclusion Criteria:

* Previous treatment with bortezomib, thalidomide, or lenalidomide
* Sensory neuropathy grade III or neuropathic pain grade II
* Severe concomitant disorder, e.g. other malignancy or severe heart disease
* Transformation to plasma cell leukemia or aggressive lymphoma
* Frequent visits for bortezomib injections not feasible
* Anticipated non-adherence to study protocol
* Pregnancy
* Anticipated non-adherence to rules for prevention of pregnancy
* Severe thrombocytopenia (Thrombocyte count less than 25000/microliter)

Primary outcomes:
measure: Progression free survival
Secondary outcomes:
measure: Response rate
measure: Response duration
measure: Time to start of other treatment
measure: Toxicity
measure: Quality of life
measure: Response rate after cross-over
measure: Response duration after cross-over
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Ålborg university Hospital
city: Herlev
country: Denmark
facility: Herlev University Hospital
city: Koebenhavn
country: Denmark
facility: Rigshospitalet
city: Odense
country: Denmark
facility: Odense University Hospital
city: Århus
country: Denmark
facility: Århus University Hospital
city: Oslo
country: Norway
facility: Ullevål Sykehus
city: Oslo
country: Norway
facility: Diakonhjemmet
city: Stavanger
country: Norway
facility: Stavanger Universitetssykehus
city: Trondheim
country: Norway
facility: Trondheim University Hospital
city: Falun
country: Sweden
facility: Falun Hospital
city: Gävle
country: Sweden
facility: Gävle Hospital
city: Göteborg
country: Sweden
facility: Sahlgrenska University Hospital
city: Helsingborg
country: Sweden
facility: Helsingborg Hospital
city: Lidköping
country: Sweden
facility: Lidköping Hospital
city: Lund
country: Sweden
facility: Lund University Hospital
city: Malmö
country: Sweden
facility: Malmö University Hospital
city: Mölndal
country: Sweden
facility: Mölndal hospital
city: Skövde
country: Sweden
facility: Skövde Hospital
city: Stockholm
country: Sweden
facility: St Göran Hospital
city: Sundsvall
country: Sweden
facility: Sundsvall Hospital
city: Uddevalla
country: Sweden
facility: Uddevalla Hospital
city: Umeå
country: Sweden
facility: Norrland University Hospital
city: Uppsala
country: Sweden
facility: Uppsala University Hospital
city: Västerås
country: Sweden
facility: Västerås Hospital
city: Växjö
country: Sweden
facility: Växjö Hospital
city: Örebro
country: Sweden
facility: Örebro University Hospital
city: Örnsköldsvik
country: Sweden
facility: Örnsköldsvik Hospital
Study officials:
affiliation: Department of Medicine, Lidköping Hospital, S-53185 Lidköping, Sweden
name: Martin Hjorth, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: