Clinical trial NCT00417911: Efficacy of Bortezomib Consolidation After High-dose Melphalan With Stem Cell Support in Myeloma Patients
Official title: Clinical Protocol Bortezomib Consolidation in Patients With Myeloma Following Treatment With High-dose Melphalan and Autologous Stem Cell Support. A Randomised NMSG Trial (15/05)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Myeloma
Keywords: multiple myeloma
autologous stem cell transplantation
high-dose melphalan
bortezomib
consolidation
event free survival
phase III
Lead sponsor: Nordic Myeloma Study Group
Sponsor class: OTHER
Collaborators: name: Janssen-Cilag Ltd.
First posted: 2007-01-04
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: 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
timeFrame: 1 year after randomization of the last patient
Secondary outcomes:
measure: Overall survival from ASCT
measure: Overall survival from start of relapse treatment
measure: Time to need for relapse treatment
measure: Response rate in patients not in CR following ASCT
measure: Toxicity from consolidation treatment
measure: Quality of life
measure: Cost utility
measure: Planned subgroup analysis: comparison of primary and secondary endpoint in patients receiving one vs. two high dose treatments
Other outcomes:
Locations:
city: Herlev
country: Denmark
facility: Hæmatologisk afdeling L Amtssygehuset i Herlev
city: København Ø
country: Denmark
facility: Medicinsk Hæmatologisk afd L4042, Rigshospitalet
city: Odense C
country: Denmark
facility: Hæmatologisk afd X, Odense Universitetshospital
city: Ålborg
country: Denmark
facility: Hæmatologisk afdeling B, Aalborg Sygehus Syd
city: Århus C
country: Denmark
facility: Hæmatologisk afd. B, Århus Universitetshospital, Amtssygehuset
city: Tampere
country: Finland
facility: Tampere University Hospital, Dep 10a
city: Turku
country: Finland
facility: Turku University Hospital, Dept. of Medicine, PL 52,
city: Reykjavik
country: Iceland
facility: Hemathology department, University State Hospital, Landspitali
city: Bergen
country: Norway
facility: Hematologisk seksjon, med avd, Haukeland Universitetssykehus
city: Oslo
country: Norway
facility: Seksjon for blodsykdommer, Med. avd.,Rikshospitalet
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 Regionssykehuset
city: Huddinge
country: Sweden
facility: Hematologiska klin, Huddinge sjukhus
city: Linköping
country: Sweden
facility: Hematologkliniken, Universitetssjukhuset
city: Lund
country: Sweden
facility: University Hospital Lund
city: Malmö
country: Sweden
facility: Medicinklin, Universitetssjukhuset MAS,
city: Umeå
country: Sweden
facility: Medicinklin, sekt för hematologi, Norrlands Universitetssjukhus
city: Uppsala
country: Sweden
facility: Medicinklin, Akademiska sjukhuset
city: Örebro
country: Sweden
facility: Medicinkliniken, Universitetssjukhuset
Study officials:
affiliation: NMSG
name: Ulf-Henrik Mellqvist, Dr., PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.