Efficacy of Bortezomib Consolidation After High-dose Melphalan With Stem Cell Support in Myeloma Patients

NCT ID: NCT00417911

Last Updated: 2010-06-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-12-31
• Study Completion Date: 2010-05-31

Brief Summary

Multiple myeloma is a malignant incurable hematological disease where survival has been significantly improved by high-dose melphalan with autologous stem cell support (ASCT) in younger patients. However, the disease will eventually relapse and new treatment is demanded. Bortezomib is a newly approved drug for treating relapsing multiple myeloma. It has a different biological effect and response even in patients refractory to conventional chemotherapy. The purpose of the study is in a randomized design to investigate if addition of bortezomib by 20 injections during a 4 months period starting 3 month after ASCT can prolong the time to progression compared to patients receiving no consolidation or maintenance therapy.

Detailed Description

Rationale:

ASCT prolongs EFS and OS for myeloma patients < 65 years of age. During the period from ASCT to progression most myeloma patients experience few symptoms and have a good quality of life11. A further prolongation of EFS would be a big step forward in myeloma treatment. Bortezomib is a new promising agent, which has shown clear anti-myeloma effect in heavily pre-treated patients. After ASCT the tumour cell burden is low and it is the hypothesis of this clinical trial that the unique mechanism of action of bortezomib may reduce the number of tumour cells even further and by doing so prolong EFS.

Primary objective:

• Evaluate the effect on EFS (an event is defined as either progression or death of any cause without preceding progression) of consolidation treatment with bortezomib after ASCT compared to no consolidation

Secondary objectives:

• Overall survival from ASCT
• Overall survival from start of relapse treatment
• Time to need for relapse treatment
• Response rate in patients not in CR following ASCT
• Toxicity from consolidation treatment
• Quality of life
• Cost utility
• Planned subgroup analysis: comparison of primary and secondary endpoint in patients receiving one vs. two high dose treatments

Conditions

Multiple Myeloma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

No treatment

Group Type: ACTIVE_COMPARATOR

bortezomib

Intervention Type: DRUG

Bortezomib 1,3 mg/sqm Days 1,4,8,11 for two 3-week cycles and then once a week for three weeks in 4 4-week cycles

Bortezomib consolidation

Bortezomib consolidation : 20 injections starting 3 months after ASCT

Group Type: EXPERIMENTAL

bortezomib

Intervention Type: DRUG

Bortezomib 1,3 mg/sqm Days 1,4,8,11 for two 3-week cycles and then once a week for three weeks in 4 4-week cycles

Interventions

bortezomib

Bortezomib 1,3 mg/sqm Days 1,4,8,11 for two 3-week cycles and then once a week for three weeks in 4 4-week cycles

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Symptomatic myeloma diagnosis according to criteria in attachment 3
• ASCT is performed or has been performed in the last five weeks (time limit two weeks for patients randomised at 2nd transplantation) as a part of primary therapy
• Signed informed consent given prior to any study related activities have been performed

Exclusion Criteria

• Prior exposure to bortezomib
• Allogeneic transplantation scheduled as a part of the primary treatment
• Neuropathy > Grade 2 (neurological symptoms interfering with ADL)
• Non-secreting myeloma
• Other concurrent disease making bortezomib treatment unsuitable
• Positive pregnancy test (only applicable for women with childbearing potential)
• Has known or suspected hypersensitivity or intolerance to boron, mannitol, or heparin, if an indwelling catheter is used
• Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrolment, New York Heart Association (NYHA) Class III or IV heart failure (Attachment 6, NYHA Classification of Cardiac Disease), uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis
• History of hypotension or has decreased blood pressure (sitting systolic blood pressure [SBP] £100 mmHg and/or sitting diastolic blood pressure [DBP] £60 mmHg)
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study
• Have received an experimental drug or used an experimental medical device within 4 weeks prior to inclusion into the study

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen-Cilag Ltd.

INDUSTRY

Sponsor Role: collaborator

Nordic Myeloma Study Group

OTHER

Sponsor Role: lead

Responsible Party

Nordic Myeloma Study Group, Sahlgrenska University Hospital Gothenborg

Principal Investigators

Ulf-Henrik Mellqvist, Dr., PhD

Role: PRINCIPAL_INVESTIGATOR

NMSG

Locations

Hæmatologisk afdeling B, Aalborg Sygehus Syd

Aalborg, , Denmark

Hæmatologisk afd. B, Århus Universitetshospital, Amtssygehuset

Århus C, , Denmark

Hæmatologisk afdeling L Amtssygehuset i Herlev

Herlev, , Denmark

Medicinsk Hæmatologisk afd L4042, Rigshospitalet

København Ø, , Denmark

Hæmatologisk afd X, Odense Universitetshospital

Odense C, , Denmark

Tampere University Hospital, Dep 10a

Tampere, , Finland

Turku University Hospital, Dept. of Medicine, PL 52,

Turku, , Finland

Hemathology department, University State Hospital, Landspitali

Reykjavik, , Iceland

Hematologisk seksjon, med avd, Haukeland Universitetssykehus

Bergen, , Norway

Seksjon for blodsykdommer, Med. avd.,Rikshospitalet

Oslo, , Norway

Hematologisk avdeling Ullevål Sykehus

Oslo, , Norway

Med avd B, Hematologisk seksjon, Universitetssykehuset Nord Norge

Tromsø, , Norway

Hematologisk seksjon Regionssykehuset

Trondheim, , Norway

Hematologiska klin, Huddinge sjukhus

Huddinge, , Sweden

Hematologkliniken, Universitetssjukhuset

Linköping, , Sweden

University Hospital Lund

Lund, , Sweden

Medicinklin, Universitetssjukhuset MAS,

Malmo, , Sweden

Medicinkliniken, Universitetssjukhuset

Örebro, , Sweden

Medicinklin, sekt för hematologi, Norrlands Universitetssjukhus

Umeå, , Sweden

Medicinklin, Akademiska sjukhuset

Uppsala, , Sweden

Countries

Denmark; Finland; Iceland; Norway; Sweden

References

Mellqvist UH, Gimsing P, Hjertner O, Lenhoff S, Laane E, Remes K, Steingrimsdottir H, Abildgaard N, Ahlberg L, Blimark C, Dahl IM, Forsberg K, Gedde-Dahl T, Gregersen H, Gruber A, Guldbrandsen N, Haukas E, Carlson K, Kvam AK, Nahi H, Lindas R, Andersen NF, Turesson I, Waage A, Westin J; Nordic Myeloma Study Group. Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma: a Nordic Myeloma Study Group randomized phase 3 trial. Blood. 2013 Jun 6;121(23):4647-54. doi: 10.1182/blood-2012-11-464503. Epub 2013 Apr 24.

Reference Type: DERIVED

PMID: 23616624 (View on PubMed)

Other Identifiers

EudraCT No: 2005-002756-18

Identifier Type: -

Identifier Source: secondary_id

NMSG 15/05

Identifier Type: -

Identifier Source: org_study_id