Bortezomib and High-dose Melphalan at Myeloma Relapse

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00508209
Recruitment Status : Unknown
Verified June 2010 by Nordic Myeloma Study Group.
Recruitment status was:  Active, not recruiting
First Posted : July 27, 2007
Last Update Posted : June 22, 2010
Janssen-Cilag Ltd.
Information provided by:
Nordic Myeloma Study Group

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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: bortezomib Phase 2

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).

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : July 2007
Actual Primary Completion Date : June 2009
Estimated Study Completion Date : September 2010

Intervention Details:
  • Drug: bortezomib
    1.3 mg/sqm days -5 and -2 in connection with high-dose melphalan (200mg/sqm day -2) and autologous stem cell support
    Other Name: Velcade

Primary Outcome Measures :
  1. 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 Measures :
  1. Determining the toxicity of bortezomib as part of the high-dose melphalan conditioning [ Time Frame: 3 years ]
  2. Response rate of the second ASCT [ Time Frame: 3 years ]
  3. Marrow regeneration [ Time Frame: 3 years ]
  4. OS compared with the OS of matched controls from the former NMSG [ Time Frame: 3 years ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00508209

Department of Haematology B, Aalborg Hospital, University of Aarhus
Aalborg, Denmark, 9000
Department of Haematology, Herlev University Hospital
Herlev, Denmark, 2730
Department of Haematology X, Odense University Hospital
Odense, Denmark, 5000
Dept. of Haematology, Århus University Hospital
Århus, Denmark, 8000
Hematologisk seksjon, med avd, Haukeland Universitetssykehus
Bergen, Norway, N-5021
Department of Hematology, Rikshospitalet
Oslo, Norway
Hematologisk seksjon, St.Olav Hospital
Trondheim, Norway, N-7006
Department of Hematology, Sahlgrenska Sjukhuset
Göteborg, Sweden
University Hospital Lund
Lund, Sweden, SE-221 85
Sponsors and Collaborators
Nordic Myeloma Study Group
Janssen-Cilag Ltd.
Principal Investigator: Peter Gimsing, M.D. Department of Haematology, Rigshospitalet

Responsible Party: Peter Gimsing, Nordic Myeloma Study Group, Rigshospitalet Identifier: NCT00508209     History of Changes
Other Study ID Numbers: NMSG 16-07
EudraCT nr 2006-007022-64
KF 02 2006-7206
LMS 2612-3390
First Posted: July 27, 2007    Key Record Dates
Last Update Posted: June 22, 2010
Last Verified: June 2010

Keywords provided by Nordic Myeloma Study Group:
high-dose melphalan

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Disease Attributes
Pathologic Processes
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs