Bortezomib and High-dose Melphalan at Myeloma Relapse

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00508209
• Other study ID #: NMSG 16-07
• Secondary ID: EudraCT nr 2006-
• Status: Active, not recruiting
• Phase: Phase 2
• First received: July 26, 2007
• Last updated: June 17, 2010
• Start date: July 2007
• Est. completion date: September 2010

Study information

• Verified date: June 2010
• Source: Nordic Myeloma Study Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Medicines Agency
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 50
• Est. completion date: September 2010
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma

Intervention

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

Locations

Country	Name	City	State
Denmark	Department of Haematology B, Aalborg Hospital, University of Aarhus	Aalborg
Denmark	Dept. of Haematology, Århus University Hospital	Århus
Denmark	Department of Haematology, Herlev University Hospital	Herlev
Denmark	Department of Haematology X, Odense University Hospital	Odense
Norway	Hematologisk seksjon, med avd, Haukeland Universitetssykehus	Bergen
Norway	Department of Hematology, Rikshospitalet	Oslo
Norway	Hematologisk seksjon, St.Olav Hospital	Trondheim
Sweden	Department of Hematology, Sahlgrenska Sjukhuset	Göteborg
Sweden	University Hospital Lund	Lund

Sponsors (2)

Lead Sponsor	Collaborator
Nordic Myeloma Study Group	Janssen-Cilag Ltd.

Countries where clinical trial is conducted

Denmark,  Norway,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		3 years	No
Secondary	Determining the toxicity of bortezomib as part of the high-dose melphalan conditioning		3 years	Yes
Secondary	Response rate of the second ASCT		3 years	No
Secondary	Marrow regeneration		3 years	Yes
Secondary	OS compared with the OS of matched controls from the former NMSG		3 years	No