Thalidomide Versus Bortezomib in Melphalan Refractory Myeloma

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma	Drug: Bortezomib; Drug: Thalidomide	Phase 3

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	300 participants
Allocation:	Randomized
Intervention Model:	Crossover Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Thalidomide Versus Bortezomib in Melphalan Refractory Myeloma
Study Start Date :	October 2007
Actual Primary Completion Date :	September 2010
Actual Study Completion Date :	December 2010

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Active Comparator: 1; Bortezomib - dexamethasone	Drug: Bortezomib; Bortezomib 1,3 mg/m2 intravenously on days 1, 4, 8 och 11 of every 3 weeks cycle until maximal response, toxicity or maximum 8 cycles Dexamethasone 20 mg days 1-2, 4-5, 8-9 and 11-12 during the first 2 cycles, thereafter individualized dose depending on response and toxicity
Experimental: 2; Thalidomide - dexamethasone	Drug: Thalidomide; Thalidomide 50 mg/day with dose escalation every 3 weeks until response or toxicity, maximal dose 200 mg/day Dexamethasone 40 mg/day day 1-4 every 3 weeks for at least 2 courses, thereafter individualized dose depending on response and toxicity

Outcome Measures

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Primary Outcome Measures :

1. Progression free survival [ Time Frame: Not specified ]

Secondary Outcome Measures :

1. Response rate [ Time Frame: Not specified ]
2. Response duration [ Time Frame: Not specified ]
3. Time to start of other treatment [ Time Frame: Not specified ]
4. Toxicity [ Time Frame: Not specified ]
5. Quality of life [ Time Frame: Not specified ]
6. Response rate after cross-over [ Time Frame: Not specified ]
7. Response duration after cross-over [ Time Frame: Not specified ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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)

Contacts and Locations

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Locations

Denmark
Ålborg university Hospital
Aalborg, Denmark, 9000
Herlev University Hospital
Herlev, Denmark, 2730
Rigshospitalet
Koebenhavn, Denmark, 2100
Odense University Hospital
Odense, Denmark, 5000
Århus University Hospital
Århus, Denmark, 8000
Norway
Ullevål Sykehus
Oslo, Norway, 0407
Diakonhjemmet
Oslo, Norway
Stavanger Universitetssykehus
Stavanger, Norway, 4068
Trondheim University Hospital
Trondheim, Norway, N-7006
Sweden
Falun Hospital
Falun, Sweden, 79182
Gävle Hospital
Gävle, Sweden, 80187
Sahlgrenska University Hospital
Göteborg, Sweden, 41345
Helsingborg Hospital
Helsingborg, Sweden, 25187
Lidköping Hospital
Lidköping, Sweden, 53185
Lund University Hospital
Lund, Sweden, 22185
Malmö University Hospital
Malmö, Sweden, 20502
Mölndal hospital
Mölndal, Sweden, 43180
Skövde Hospital
Skövde, Sweden, 54185
St Göran Hospital
Stockholm, Sweden, 11281
Sundsvall Hospital
Sundsvall, Sweden, 85186
Uddevalla Hospital
Uddevalla, Sweden, 45180
Norrland University Hospital
Umeå, Sweden, 90185
Uppsala University Hospital
Uppsala, Sweden, 75185
Västerås Hospital
Västerås, Sweden, 72189
Växjö Hospital
Växjö, Sweden, 35185
Örebro University Hospital
Örebro, Sweden, 70185
Örnsköldsvik Hospital
Örnsköldsvik, Sweden, 89189

Sponsors and Collaborators

Nordic Myeloma Study Group

Investigators

Principal Investigator:	Martin Hjorth, MD, PhD	Department of Medicine, Lidköping Hospital, S-53185 Lidköping, Sweden

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Martin Hjorth, Department of Medicine, Lidköping Hospital, S-53185 Lidköping, Sweden
ClinicalTrials.gov Identifier:	NCT00602511 History of Changes
Other Study ID Numbers:	NMSG 17/07; EudraCT no. 2007-001292-11
First Posted:	January 28, 2008
Last Update Posted:	February 9, 2011
Last Verified:	February 2011

Keywords provided by Nordic Myeloma Study Group:

Melfalan refractory multiple myeloma; Multiple myeloma; Relapsing; Refractory	Thalidomide; Bortezomib; Randomized clinical trial

Additional relevant MeSH terms:

Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Dexamethasone acetate	Dexamethasone; Bortezomib; Melphalan; Thalidomide; BB 1101; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal