Thalidomide Versus Bortezomib in Melphalan Refractory Myeloma

Condition(s) targeted: Multiple Myeloma

Intervention: Bortezomib (Drug); Thalidomide (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Nordic Myeloma Study Group

Official(s) and/or principal investigator(s):
Martin Hjorth, MD, PhD, Principal Investigator, Affiliation: Department of Medicine, Lidköping Hospital, S-53185 Lidköping, Sweden

Overall contact:
Martin Hjorth, MD, PhD, Phone: +46 510 85000, Email: martin.hjorth@vgregion.se

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.

Official title: Thalidomide Versus Bortezomib in Melphalan Refractory Myeloma

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Progression free survival

Secondary outcome:

Response rate

Response duration

Time to start of other treatment

Toxicity

Quality of life

Response rate after cross-over

Response duration after cross-over

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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)

Martin Hjorth, MD, PhD, Phone: +46 510 85000, Email: martin.hjorth@vgregion.se

Ålborg university Hospital, Aalborg 9000, Denmark; Recruiting
Henrik Gregersen, MD, Principal Investigator

Herlev University Hospital, Herlev 2730, Denmark; Recruiting
Annette Vangsted, MD, PhD, Principal Investigator

Rigshospitalet, Koebenhavn 2100, Denmark; Recruiting
Peter Gimsing, MD, PhD, Principal Investigator

Odense University Hospital, Odense 5000, Denmark; Recruiting
Per Per, MD, Principal Investigator

Århus University Hospital, Århus 8000, Denmark; Recruiting
Nils Frost Andersen, MD, Principal Investigator

Diakonhjemmet, Oslo, Norway; Recruiting
Fredrik Schjesvold, MD, Principal Investigator

Ullevål Sykehus, Oslo 0407, Norway; Recruiting
Nina Gulbrandsen, MD, PhD, Principal Investigator

Stavanger Universitetssykehus, Stavanger 4068, Norway; Recruiting
Einar Haukås, MD, Principal Investigator

Trondheim University Hospital, Trondheim N-7006, Norway; Recruiting
Öyvind Hjertner, MD, PhD, Principal Investigator

Falun Hospital, Falun 79182, Sweden; Recruiting
Max Flogegård, MD, Principal Investigator

Gävle Hospital, Gävle 80187, Sweden; Recruiting
Annika Othzén, MD, Principal Investigator

Sahlgrenska University Hospital, Göteborg 41345, Sweden; Recruiting
Ulf-Henrik Mellqvist, MD, PhD, Principal Investigator

Helsingborg Hospital, Helsingborg 25187, Sweden; Recruiting
Per Axelsson, MD, Principal Investigator

Lidköping Hospital, Lidköping 53185, Sweden; Recruiting
Sven Erdal, MD, Principal Investigator

Lund University Hospital, Lund 22185, Sweden; Recruiting
Stig Lenhoff, MD, PhD, Principal Investigator

Malmö University Hospital, Malmö 20502, Sweden; Recruiting
Elena Holm, MD, Principal Investigator

Mölndal hospital, Mölndal 43180, Sweden; Withdrawn

Skövde Hospital, Skövde 54185, Sweden; Recruiting
Rolf Billström, MD, PhD, Principal Investigator

St Göran Hospital, Stockholm 11281, Sweden; Recruiting
Torbjörn Karlsson, MD, Principal Investigator

Sundsvall Hospital, Sundsvall 85186, Sweden; Recruiting
Maria Strandberg, MD, Principal Investigator

Uddevalla Hospital, Uddevalla 45180, Sweden; Recruiting
Björn Andréasson, MD, PhD, Principal Investigator

Norrland University Hospital, Umeå 90185, Sweden; Recruiting
Karin Forsberg, MD, Principal Investigator

Uppsala University Hospital, Uppsala 75185, Sweden; Recruiting
Kristina Carlson, MD, PhD, Principal Investigator

Västerås Hospital, Västerås 72189, Sweden; Recruiting
Torbjörn Karlsson, MD, Principal Investigator

Växjö Hospital, Växjö 35185, Sweden; Recruiting
Margaretha S Carlsson, MD, Principal Investigator

Örebro University Hospital, Örebro 70185, Sweden; Recruiting
Olle Linder, MD, Principal Investigator

Örnsköldsvik Hospital, Örnsköldsvik 89189, Sweden; Recruiting
Kjell Lundkvist, MD, Principal Investigator

Starting date: October 2007
Last updated: June 30, 2010