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

June 17, 2010 updated by: Nordic Myeloma Study Group

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)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Anticipated)

400

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Herlev, Denmark, DK-2730
        • Hæmatologisk afdeling L Amtssygehuset i Herlev
      • København Ø, Denmark, DK-2100
        • Medicinsk Hæmatologisk afd L4042, Rigshospitalet
      • Odense C, Denmark, DK-5000
        • Hæmatologisk afd X, Odense Universitetshospital
      • Ålborg, Denmark, DK-9000
        • Hæmatologisk afdeling B, Aalborg Sygehus Syd
      • Århus C, Denmark, DK-8000
        • Hæmatologisk afd. B, Århus Universitetshospital, Amtssygehuset
  • Finland
      • Tampere, Finland, SF-33 521
        • Tampere University Hospital, Dep 10a
      • Turku, Finland, SF-20521
        • Turku University Hospital, Dept. of Medicine, PL 52,
  • Iceland
      • Reykjavik, Iceland, 101
        • Hemathology department, University State Hospital, Landspitali
  • Norway
      • Bergen, Norway, N-5021
        • Hematologisk seksjon, med avd, Haukeland Universitetssykehus
      • Oslo, Norway, N - 0407
        • Hematologisk avdeling Ullevål Sykehus
      • Oslo, Norway, N - 0027
        • Seksjon for blodsykdommer, Med. avd.,Rikshospitalet
      • Tromsø, Norway, N-9038
        • Med avd B, Hematologisk seksjon, Universitetssykehuset Nord Norge
      • Trondheim, Norway, N - 7006
        • Hematologisk seksjon Regionssykehuset
  • Sweden
      • Huddinge, Sweden, SE-141 86
        • Hematologiska klin, Huddinge sjukhus
      • Linköping, Sweden, SE-581 85
        • Hematologkliniken, Universitetssjukhuset
      • Lund, Sweden, SE-221 85
        • University Hospital Lund
      • Malmö, Sweden, SE-205 02
        • Medicinklin, Universitetssjukhuset MAS,
      • Umeå, Sweden, SE-901 85
        • Medicinklin, sekt för hematologi, Norrlands Universitetssjukhus
      • Uppsala, Sweden, SE-751 85
        • Medicinklin, Akademiska sjukhuset
      • Örebro, Sweden, SE-70185
        • Medicinkliniken, Universitetssjukhuset

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: No treatment
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
Experimental: Bortezomib consolidation
Bortezomib consolidation : 20 injections starting 3 months after ASCT
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
Time Frame: 1 year after randomization of the last patient
1 year after randomization of the last patient

Secondary Outcome Measures

Outcome Measure
Quality of life
Cost utility
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
Planned subgroup analysis: comparison of primary and secondary endpoint in patients receiving one vs. two high dose treatments

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nordic Myeloma Study Group

Collaborators

Janssen-Cilag Ltd.

Investigators

  • Principal Investigator: Ulf-Henrik Mellqvist, Dr., PhD, NMSG

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2005

Primary Completion (Actual)

May 1, 2009

Study Completion (Actual)

May 1, 2010

Study Registration Dates

First Submitted

January 3, 2007

First Submitted That Met QC Criteria

January 3, 2007

First Posted (Estimate)

January 4, 2007

Study Record Updates

Last Update Posted (Estimate)

June 22, 2010

Last Update Submitted That Met QC Criteria

June 17, 2010

Last Verified

June 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NMSG 15/05
  • EudraCT No: 2005-002756-18

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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