Bortezomib and High-dose Melphalan at Myeloma Relapse

June 17, 2010 updated by: Nordic Myeloma Study Group

Phase II Study of Bortezomib Dexamethasone and High-dose Melphalan in Patients With Relapse After High-dose Melphalan With Autologous Stem Cell Support

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.

Study Overview

Status

Unknown

Conditions

Multiple Myeloma

Intervention / Treatment

Drug: bortezomib

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

Enrollment (Anticipated)

Phase

Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Denmark
- - Aalborg, Denmark, 9000
    - Department of Haematology B, Aalborg Hospital, University of Aarhus
  - Herlev, Denmark, 2730
    - Department of Haematology, Herlev University Hospital
  - Odense, Denmark, 5000
    - Department of Haematology X, Odense University Hospital
  - Århus, Denmark, 8000
    - Dept. of Haematology, Århus University Hospital
Norway
- - Bergen, Norway, N-5021
    - Hematologisk seksjon, med avd, Haukeland Universitetssykehus
  - Oslo, Norway
    - Department of Hematology, Rikshospitalet
  - Trondheim, Norway, N-7006
    - Hematologisk seksjon, St.Olav Hospital
Sweden
- - Göteborg, Sweden
    - Department of Hematology, Sahlgrenska Sjukhuset
  - Lund, Sweden, SE-221 85
    - University Hospital Lund

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Interventional Model: Single Group Assignment
Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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	3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Determining the toxicity of bortezomib as part of the high-dose melphalan conditioning Time Frame: 3 years	3 years
Response rate of the second ASCT Time Frame: 3 years	3 years
Marrow regeneration Time Frame: 3 years	3 years
OS compared with the OS of matched controls from the former NMSG Time Frame: 3 years	3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nordic Myeloma Study Group

Collaborators

Janssen-Cilag Ltd.

Investigators

Principal Investigator: Peter Gimsing, M.D., Department of Haematology, Rigshospitalet

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2007

Primary Completion (Actual)

June 1, 2009

Study Completion (Anticipated)

September 1, 2010

Study Registration Dates

First Submitted

July 26, 2007

First Submitted That Met QC Criteria