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

Multiple Myeloma Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00417911
• Other study ID #: NMSG 15/05
• Secondary ID: EudraCT No: 2005
• Status: Completed
• Phase: Phase 3
• First received: January 3, 2007
• Last updated: June 17, 2010
• Start date: December 2005
• Est. completion date: May 2010

Study information

• Verified date: June 2010
• Source: Nordic Myeloma Study Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: Sweden: Medical Products AgencySweden: Regional Ethical Review Board
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 400
• Est. completion date: May 2010
• Est. primary completion date: May 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• 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

Locations

Country	Name	City	State
Denmark	Hæmatologisk afdeling B, Aalborg Sygehus Syd	Ålborg
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
Finland	Tampere University Hospital, Dep 10a	Tampere
Finland	Turku University Hospital, Dept. of Medicine, PL 52,	Turku
Iceland	Hemathology department, University State Hospital, Landspitali	Reykjavik
Norway	Hematologisk seksjon, med avd, Haukeland Universitetssykehus	Bergen
Norway	Hematologisk avdeling Ullevål Sykehus	Oslo
Norway	Seksjon for blodsykdommer, Med. avd.,Rikshospitalet	Oslo
Norway	Med avd B, Hematologisk seksjon, Universitetssykehuset Nord Norge	Tromsø
Norway	Hematologisk seksjon Regionssykehuset	Trondheim
Sweden	Hematologiska klin, Huddinge sjukhus	Huddinge
Sweden	Hematologkliniken, Universitetssjukhuset	Linköping
Sweden	University Hospital Lund	Lund
Sweden	Medicinklin, Universitetssjukhuset MAS,	Malmö
Sweden	Medicinkliniken, Universitetssjukhuset	Örebro
Sweden	Medicinklin, sekt för hematologi, Norrlands Universitetssjukhus	Umeå
Sweden	Medicinklin, Akademiska sjukhuset	Uppsala

Sponsors (2)

Lead Sponsor	Collaborator
Nordic Myeloma Study Group	Janssen-Cilag Ltd.

Countries where clinical trial is conducted

Denmark,  Finland,  Iceland,  Norway,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		1 year after randomization of the last patient	Yes
Secondary	Overall survival from ASCT
Secondary	Overall survival from start of relapse treatment
Secondary	Time to need for relapse treatment
Secondary	Response rate in patients not in CR following ASCT
Secondary	Toxicity from consolidation treatment
Secondary	Quality of life
Secondary	Cost utility
Secondary	Planned subgroup analysis: comparison of primary and secondary endpoint in patients receiving one vs. two high dose treatments

External Links

•   NMSG home page