Clinical trial NCT00508209: 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
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: high-dose melphalan
bortezomib
response
toxicity
relapse
Lead sponsor: Nordic Myeloma Study Group
Sponsor class: OTHER
Collaborators: name: Janssen-Cilag Ltd.
First posted: 2007-07-27
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: 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
timeFrame: 3 years
Secondary outcomes:
measure: Determining the toxicity of bortezomib as part of the high-dose melphalan conditioning
timeFrame: 3 years
measure: Response rate of the second ASCT
timeFrame: 3 years
measure: Marrow regeneration
timeFrame: 3 years
measure: OS compared with the OS of matched controls from the former NMSG
timeFrame: 3 years
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Department of Haematology B, Aalborg Hospital, University of Aarhus
city: Herlev
country: Denmark
facility: Department of Haematology, Herlev University Hospital
city: Odense
country: Denmark
facility: Department of Haematology X, Odense University Hospital
city: Århus
country: Denmark
facility: Dept. of Haematology, Århus University Hospital
city: Bergen
country: Norway
facility: Hematologisk seksjon, med avd, Haukeland Universitetssykehus
city: Oslo
country: Norway
facility: Department of Hematology, Rikshospitalet
city: Trondheim
country: Norway
facility: Hematologisk seksjon, St.Olav Hospital
city: Göteborg
country: Sweden
facility: Department of Hematology, Sahlgrenska Sjukhuset
city: Lund
country: Sweden
facility: University Hospital Lund
Study officials:
affiliation: Department of Haematology, Rigshospitalet
name: Peter Gimsing, M.D.
role: PRINCIPAL_INVESTIGATOR
References: