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

Phase 3
Completed
Conditions
Multiple Myeloma
Interventions
Registration Number
NCT00417911
Lead Sponsor
Nordic Myeloma Study Group
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

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
400
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

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
No treatmentbortezomib-
Bortezomib consolidationbortezomibBortezomib consolidation : 20 injections starting 3 months after ASCT
Primary Outcome Measures
NameTimeMethod
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 consolidation1 year after randomization of the last patient
Secondary Outcome Measures
NameTimeMethod
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

Trial Locations

Locations (20)

Hæmatologisk afdeling L Amtssygehuset i Herlev

🇩🇰

Herlev, Denmark

Medicinklin, sekt för hematologi, Norrlands Universitetssjukhus

🇸🇪

Umeå, Sweden

University Hospital Lund

🇸🇪

Lund, Sweden

Hæmatologisk afdeling B, Aalborg Sygehus Syd

🇩🇰

Ålborg, Denmark

Medicinklin, Universitetssjukhuset MAS,

🇸🇪

Malmö, Sweden

Hæmatologisk afd. B, Århus Universitetshospital, Amtssygehuset

🇩🇰

Århus C, Denmark

Hematologiska klin, Huddinge sjukhus

🇸🇪

Huddinge, Sweden

Hematologkliniken, Universitetssjukhuset

🇸🇪

Linköping, Sweden

Medicinkliniken, Universitetssjukhuset

🇸🇪

Örebro, Sweden

Hemathology department, University State Hospital, Landspitali

🇮🇸

Reykjavik, Iceland

Hematologisk seksjon, med avd, Haukeland Universitetssykehus

🇳🇴

Bergen, Norway

Medicinsk Hæmatologisk afd L4042, Rigshospitalet

🇩🇰

København Ø, Denmark

Hæmatologisk afd X, Odense Universitetshospital

🇩🇰

Odense C, Denmark

Medicinklin, Akademiska sjukhuset

🇸🇪

Uppsala, Sweden

Tampere University Hospital, Dep 10a

🇫🇮

Tampere, Finland

Hematologisk avdeling Ullevål Sykehus

🇳🇴

Oslo, Norway

Med avd B, Hematologisk seksjon, Universitetssykehuset Nord Norge

🇳🇴

Tromsø, Norway

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

🇫🇮

Turku, Finland

Seksjon for blodsykdommer, Med. avd.,Rikshospitalet

🇳🇴

Oslo, Norway

Hematologisk seksjon Regionssykehuset

🇳🇴

Trondheim, Norway

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