Bortezomib and High-dose Melphalan at Myeloma Relapse
Bortezomib and High-dose Melphalan at Myeloma Relapse
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.
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).
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