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

Sponsor:	Nordic Myeloma Study Group
Collaborator:	Janssen-Cilag Ltd.
Information provided by:	Nordic Myeloma Study Group
ClinicalTrials.gov Identifier:	NCT00417911

Purpose

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.

Condition	Intervention	Phase
Multiple Myeloma	Drug: bortezomib	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
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)

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Multiple Myeloma

Drug Information available for: Bortezomib Melphalan Sarcolysin Melphalan hydrochloride

U.S. FDA Resources

Further study details as provided by Nordic Myeloma Study Group:

Primary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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

Estimated Enrollment:	400
Study Start Date:	December 2005
Study Completion Date:	May 2010
Primary Completion Date:	May 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00417911

Locations

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

Sponsors and Collaborators

Nordic Myeloma Study Group

Janssen-Cilag Ltd.

Investigators

Principal Investigator:

Ulf-Henrik Mellqvist, Dr., PhD

NMSG

More Information

Additional Information:

NMSG home page This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Ulf-Henrik Melqvist, Nordic Myeloma Study Group, Sahlgrenska University Hospital Gothenborg
ClinicalTrials.gov Identifier:	NCT00417911 History of Changes
Other Study ID Numbers:	NMSG 15/05, EudraCT No: 2005-002756-18
Study First Received:	January 3, 2007
Last Updated:	June 17, 2010
Health Authority:	Sweden: Medical Products Agency; Sweden: Regional Ethical Review Board

Keywords provided by Nordic Myeloma Study Group:

multiple myeloma
autologous stem cell transplantation
high-dose melphalan
bortezomib

consolidation
event free survival
phase III

Additional relevant MeSH terms:

Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases

Melphalan
Bortezomib
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Protease Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on February 09, 2012