Bortezomib and High-dose Melphalan at Myeloma Relapse
Primary Purpose
Multiple Myeloma
Status
Unknown status
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
bortezomib
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring high-dose melphalan, bortezomib, response, toxicity, relapse
Eligibility Criteria
Inclusion Criteria:
- First relapse after ASCT
- Symptomatic myeloma
- More than 2,0 x 10^6 CD34+ stem cells / kg bodyweight in the freezer for stem cell support
- Signed informed consent given prior to any study related activities have been performed
- Age > 18 years
Exclusion Criteria:
- Allogeneic transplantation scheduled as a part of the treatment
- Expected survival of less than one month.
- Performance status (WHO) > 3
- Neuropathy > Grade 3 (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 melphalan, dexamethasone, 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
Sites / Locations
- Department of Haematology B, Aalborg Hospital, University of Aarhus
- Department of Haematology, Herlev University Hospital
- Department of Haematology X, Odense University Hospital
- Dept. of Haematology, Århus University Hospital
- Hematologisk seksjon, med avd, Haukeland Universitetssykehus
- Department of Hematology, Rikshospitalet
- Hematologisk seksjon, St.Olav Hospital
- Department of Hematology, Sahlgrenska Sjukhuset
- University Hospital Lund
Outcomes
Primary Outcome Measures
Comparison of the event free survival after first high-dose melphalan with stem cell support (ASCT) and a second ASCT combined with bortezomib treatment of first relapse
Secondary Outcome Measures
Determining the toxicity of bortezomib as part of the high-dose melphalan conditioning
Response rate of the second ASCT
Marrow regeneration
OS compared with the OS of matched controls from the former NMSG
Full Information
NCT ID
NCT00508209
First Posted
July 26, 2007
Last Updated
June 17, 2010
Sponsor
Nordic Myeloma Study Group
Collaborators
Janssen-Cilag Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT00508209
Brief Title
Bortezomib and High-dose Melphalan at Myeloma Relapse
Official Title
Phase II Study of Bortezomib Dexamethasone and High-dose Melphalan in Patients With Relapse After High-dose Melphalan With Autologous Stem Cell Support
Study Type
Interventional
2. Study Status
Record Verification Date
June 2010
Overall Recruitment Status
Unknown status
Study Start Date
July 2007 (undefined)
Primary Completion Date
June 2009 (Actual)
Study Completion Date
September 2010 (Anticipated)
3. Sponsor/Collaborators
Name of the Sponsor
Nordic Myeloma Study Group
Collaborators
Janssen-Cilag Ltd.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The prognosis after retreating with high-dose melphalan with stem cell support after first relapse after high-dose treatment is dependent on the time to first relapse. Bortezomib can increase chemosensitivity of e.g. melphalan. The trial aims at determining the toxicity of adding bortezomib to high-dose melphalan with stem cell support and evaluating whether the time to a second relapse can be prolonged.
Detailed Description
Patients with multiple myeloma who have their first treatment demanding relapse after an initial treatment with high-dose melphalan with autologous stem cell support and who have more than 2.0 x 10^6 CD34+ stem cells pr kg bodyweight in the freezer can be included in the trial.
After disease status with basic clinical biochemistry, M-protein in blood and urine, bone marrow investigation including immunophenotyping and total skeletal x-ray the patients are treated with three courses of standard bortezomib (1.3 mg/sqm Days 1,4,8,11) and dexamethasone 20 mg days 1,2,4,5,8,9,11,12. Within 4 weeks the patients receive bortezomib days -5 and -2, high-dose melphalan (200 mg/sqm) day -2, and subsequent at least 2.0 x 10^6 CD34+ stem cells pr kg body weight.
The first month after high-dose therapy the patients are followed closely for toxicity according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE), Version 3.0.
The patients are evaluated for response according to EBMT criteria and for event (death or progressive disease).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
high-dose melphalan, bortezomib, response, toxicity, relapse
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
50 (Anticipated)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
bortezomib
Other Intervention Name(s)
Velcade
Intervention Description
1.3 mg/sqm days -5 and -2 in connection with high-dose melphalan (200mg/sqm day -2) and autologous stem cell support
Primary Outcome Measure Information:
Title
Comparison of the event free survival after first high-dose melphalan with stem cell support (ASCT) and a second ASCT combined with bortezomib treatment of first relapse
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Determining the toxicity of bortezomib as part of the high-dose melphalan conditioning
Time Frame
3 years
Title
Response rate of the second ASCT
Time Frame
3 years
Title
Marrow regeneration
Time Frame
3 years
Title
OS compared with the OS of matched controls from the former NMSG
Time Frame
3 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
First relapse after ASCT
Symptomatic myeloma
More than 2,0 x 10^6 CD34+ stem cells / kg bodyweight in the freezer for stem cell support
Signed informed consent given prior to any study related activities have been performed
Age > 18 years
Exclusion Criteria:
Allogeneic transplantation scheduled as a part of the treatment
Expected survival of less than one month.
Performance status (WHO) > 3
Neuropathy > Grade 3 (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 melphalan, dexamethasone, 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter Gimsing, M.D.
Organizational Affiliation
Department of Haematology, Rigshospitalet
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Haematology B, Aalborg Hospital, University of Aarhus
City
Aalborg
ZIP/Postal Code
9000
Country
Denmark
Facility Name
Department of Haematology, Herlev University Hospital
City
Herlev
ZIP/Postal Code
2730
Country
Denmark
Facility Name
Department of Haematology X, Odense University Hospital
City
Odense
ZIP/Postal Code
5000
Country
Denmark
Facility Name
Dept. of Haematology, Århus University Hospital
City
Århus
ZIP/Postal Code
8000
Country
Denmark
Facility Name
Hematologisk seksjon, med avd, Haukeland Universitetssykehus
City
Bergen
ZIP/Postal Code
N-5021
Country
Norway
Facility Name
Department of Hematology, Rikshospitalet
City
Oslo
Country
Norway
Facility Name
Hematologisk seksjon, St.Olav Hospital
City
Trondheim
ZIP/Postal Code
N-7006
Country
Norway
Facility Name
Department of Hematology, Sahlgrenska Sjukhuset
City
Göteborg
Country
Sweden
Facility Name
University Hospital Lund
City
Lund
ZIP/Postal Code
SE-221 85
Country
Sweden
12. IPD Sharing Statement
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Bortezomib and High-dose Melphalan at Myeloma Relapse
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