Clinical trial NCT00376883: Pamidronate Prophylaxis in Multiple Myeloma 30 mg/Month Versus 90 mg/Month
Official title: The Effect of i.v. Bisphosphonate on Health-Related Quality of Life and Skeletal Morbidity for Newly Diagnosed Treatment Demanding Multiple Myeloma. A Prospective Randomised Double Blinded Dose-Effective Study With Cost-Utility Analysis.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Myeloma
Keywords: multiple myeloma
pamidronate prophylaxis
dose comparison
quality of life
skeletal event
response
survival
Lead sponsor: Nordic Myeloma Study Group
Sponsor class: OTHER
Collaborators: name: Nordic Cancer Union
First posted: 2006-09-15
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Multiple myeloma is a malignant hematological disease dominated by monoclonal plasma cells in the bone marrow. Major symptoms are related to the bones due to an increased bone resorption and a decreased bone formation leading to bone pain and increased risk of fractures. The normal osteoclasts are responsible for bone degradation through stimulation from the malignant plasma cells. Bisphosphonates have been shown to inhibit the osteoclast activity but may have serious side-effects due to renal toxicity and the optimal dose have not been established.

In a randomized double blinded design it is aim to compare the standard of monthly injections of 90 mg pamidronate with 30 mg.

The primary end-point is physical function estimated by EORTC QLQ-C30 questionnaire at 12 months after starting the treatment in newly diagnosed treatment demanding multiple myeloma. Secondary end-points are skeletal related events, cost-utility analysis, response, response duration and survival and quality of life with respect to fatigue and pain.

Detailed description: Patients with newly diagnosed treatment demanding multiple myeloma are after informed consent and approved inclusion criteria randomised by telephone call to Copenhagen Trial Unit (CTU) and information on the target dose is send to the distributor, Amgros, and the local pharmacy for preparation of the pamidronate solution. Infusion is given for 2½ hours.

Before starting treatment the patient has to fulfil the first EORTC QLQ-C30 questionnaire that is send to the quality of life secretariat in Oslo, Norway. Subsequent questionnaires are mailed directly to the patients every third month.

The infusions are continued for 3 years and may be extended further upon the patient's request.

Every third month the number of skeletal event, the response and complications are recorded.

Skeletal X-rays are performed 9 and 24 months after starting the treatment.

Eligibility criteria: Inclusion Criteria:

* New diagnosed multiple myeloma with treatment demanding disease

Exclusion Criteria:

* Life-expectancy less than 3 months, another active malignant disease, treatment with bisphosphonates for more than 3 months within the last 6 months, patients with creatinine above 400 µmol/l 4 weeks after starting chemotherapy, patients who cannot cooperate for monthly infusions, patients who do not give their informed consent

Primary outcomes:
measure: Physical function at 12 months estimated by EORTC QLQ-C30 questionnaire
Secondary outcomes:
measure: Skeletal related event (time to first SRE)
measure: Cost-utility analysis
measure: Subgroup analysis (conventional chemotherapy vs. high dose chemotherapy with stem cell support)
measure: Response, recons duration, survival
measure: Quality of Life estimated by fatigue and pain according to EORTC QLQ-C30
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Department of Haematology B, Aalborg Hospital, University of Aarhus
city: Herlev
country: Denmark
facility: Department of Haematology, Herlev University Hospital
city: København Ø
country: Denmark
facility: Department of Hematology L, Rigshospitalet
city: Århus
country: Denmark
facility: Hæmatologisk afd., Århus Universitetshospital
city: Bergen
country: Norway
facility: Hematologisk seksjon, med avd, Haukeland Universitetssykehus
city: Oslo
country: Norway
facility: Hematologisk avdeling Ullevål Sykehus
city: Tromsø
country: Norway
facility: Med avd B, Hematologisk seksjon, Universitetssykehuset Nord Norge
city: Trondheim
country: Norway
facility: Hematologisk seksjon, St.Olav Hospital
city: Gothenburg
country: Sweden
facility: Sahlgrenska Universitetsjukhuset Östra
city: Linköping
country: Sweden
facility: Hematologkliniken, Universitetssjukhuset
city: Malmö
country: Sweden
facility: Medicinklin, Universitetssjukhuset MAS,
city: Umeå
country: Sweden
facility: Medicinklin, sekt för hematologi, Norrlands Universitetssjukhus
city: Uppsala
country: Sweden
facility: Medicinklinikken Akademiska sjukhuset
city: Örebro
country: Sweden
facility: Medicinkliniken, Universitetssjukhuset
Study officials:
affiliation: Nordic Myeloma Study Group
name: Peter Gimsing, Ass. prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gimsing P, Carlson K, Turesson I, Fayers P, Waage A, Vangsted A, Mylin A, Gluud C, Juliusson G, Gregersen H, Hjorth-Hansen H, Nesthus I, Dahl IM, Westin J, Nielsen JL, Knudsen LM, Ahlberg L, Hjorth M, Abildgaard N, Andersen NF, Linder O, Wisloff F. Effect of pamidronate 30 mg versus 90 mg on physical function in patients with newly diagnosed multiple myeloma (Nordic Myeloma Study Group): a double-blind, randomised controlled trial. Lancet Oncol. 2010 Oct;11(10):973-82. doi: 10.1016/S1470-2045(10)70198-4.