A Study Assessing Safety and Effectiveness of BORTEZOMIB Combination Therapy (Bortezomib + Doxorubicin Hydrochloride + Dexamethasone) in Previously Untreated Multiple Myeloma Patients
Primary Purpose
Multiple Myeloma
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Bortezomib + pegylated liposomal doxorubicin HCl + dexamethasone
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring Multiple myeloma, response rate, peripheral stem cell transplant, safety, tolerability
Eligibility Criteria
Inclusion Criteria:
- Male or female patients with newly diagnosed multiple myeloma (MM) requiring therapy for whom stem cell transplantation is considered appropriate
- Normal left ventricular ejection fraction
- Able to give voluntary written informed consent
- Female patients agree to use acceptable method for contraception
Exclusion Criteria:
- Diagnosis of smoldering multiple myeloma (asymptomatic MM with absence of lytic bone lesions)
- Renal insufficiency related to the monoclonal protein
- Diagnosis of Waldenström's disease
- Previous treatment for MM (excepting emergency use of a short course dexamethasone, radiation received > 30 days before study enrolment, plasmapheresis for treatment of clinically significant hyperviscosity syndrome > 30 days before trial enrolment)
- Major surgery within 30 days before entry
- Peripheral neuropathy or neuropathic pain Grade 2 or higher within 14 days of trial enrolment
- Uncontrolled or severe cardiovascular disease (including myocardial infarction within 6 months prior to enrollment
- NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease, cardiac amyloidosis, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities)
- Other malignancy within the past 5 years prior to enrolment (except for non-active basal cell or non-metastatic squamous cell carcinoma of the skin, cervical carcinoma in situ or Stage 1 carcinoma of the cervix
- Known HIV seropositivity or active hepatitis A, B, or C infection
- Use of any investigational drug within 30 days prior to enrolment in the trial
- Medical or psychiatric condition that could interfere with trial participation
- History of hypersensitivity or allergic reaction attributable to compounds containing boron, mannitol or doxorubicin.
Sites / Locations
Outcomes
Primary Outcome Measures
The primary endpoint was complete response (CR) and near complete response rate (nCR) post induction therapy (i.e. 4 cycles of therapy). Each cycle consisted of 21 days.
Secondary Outcome Measures
The secondary endpoints included time to best response, assessment of peripheral blood stem cells harvesting ( 3 weeks post cycle 4 day 21) and engraftment (within 4 weeks of mobilization), CR post-engraftment, QoL and safety (every cycle).
Full Information
NCT ID
NCT00561743
First Posted
November 19, 2007
Last Updated
June 7, 2011
Sponsor
Janssen-Ortho Inc., Canada
1. Study Identification
Unique Protocol Identification Number
NCT00561743
Brief Title
A Study Assessing Safety and Effectiveness of BORTEZOMIB Combination Therapy (Bortezomib + Doxorubicin Hydrochloride + Dexamethasone) in Previously Untreated Multiple Myeloma Patients
Official Title
A Phase II Study to Assess the Safety and Efficacy of DBd Combination Therapy (DOXIL/CAELYX) [Doxorubicin HCL Liposome Injection], VELCADE [Bortezomib] and Dexamethasone) for Previously Untreated Multiple Myeloma Patients
Study Type
Interventional
2. Study Status
Record Verification Date
April 2010
Overall Recruitment Status
Completed
Study Start Date
November 2005 (undefined)
Primary Completion Date
May 2007 (Actual)
Study Completion Date
May 2007 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Janssen-Ortho Inc., Canada
4. Oversight
5. Study Description
Brief Summary
The purpose of this study is to determine whether doxorubicin HCL liposome injection, bortezomib, and Dexamethasone in combination, are effective in previously untreated multiple myeloma patients. Bortezomib inhibits the function of proteasomes, a novel mechanism of action.
Detailed Description
This was a single-arm, open-label, Phase II multi-centre study in Canada only. A total of 50 newly diagnosed multiple myeloma patients who were eligible for stem cell transplant were targeted for recruitment to this study. Combination doxorubicin HCL liposome injection, bortezomib and dexamethasone induction therapy was given for 4 cycles in preparation for stem cell collection and transplant. As remission status after induction and prior to the first or second auto-transplant has been shown to be the major determinant of both event free and overall survival in multiple myeloma patients, the goal has been to improve response rates through the use of various combinational approaches. As such, the objective of the present study was to test the hypothesis that treatment with this regimen could result in a higher complete + near complete response rate (CR + nCR) prior to stem cell transplant, than obtained with current regimens, and then to confirm the response rate post-transplant. Safety was evaluated using adverse event reportings, clinical laboratory tests and tests for cardiac function (multiple-gated acquisition scan/echocardiogram and electrocardiogram). Four 21-day cycles of combination induction therapy consisting of 1.3 mg/m2 bortezomib (given i.v. Days 1, 4, 8, 11) + 30 mg/m2 Doxil/Caelyx (given i.v. Day 4) + 40 mg Dex (given po Days 1-4, 8-11, 15-18 Cycle 1 only; Days 1-4 Cycles 2-4).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Multiple myeloma, response rate, peripheral stem cell transplant, safety, tolerability
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
Bortezomib + pegylated liposomal doxorubicin HCl + dexamethasone
Primary Outcome Measure Information:
Title
The primary endpoint was complete response (CR) and near complete response rate (nCR) post induction therapy (i.e. 4 cycles of therapy). Each cycle consisted of 21 days.
Secondary Outcome Measure Information:
Title
The secondary endpoints included time to best response, assessment of peripheral blood stem cells harvesting ( 3 weeks post cycle 4 day 21) and engraftment (within 4 weeks of mobilization), CR post-engraftment, QoL and safety (every cycle).
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female patients with newly diagnosed multiple myeloma (MM) requiring therapy for whom stem cell transplantation is considered appropriate
Normal left ventricular ejection fraction
Able to give voluntary written informed consent
Female patients agree to use acceptable method for contraception
Exclusion Criteria:
Diagnosis of smoldering multiple myeloma (asymptomatic MM with absence of lytic bone lesions)
Renal insufficiency related to the monoclonal protein
Diagnosis of Waldenström's disease
Previous treatment for MM (excepting emergency use of a short course dexamethasone, radiation received > 30 days before study enrolment, plasmapheresis for treatment of clinically significant hyperviscosity syndrome > 30 days before trial enrolment)
Major surgery within 30 days before entry
Peripheral neuropathy or neuropathic pain Grade 2 or higher within 14 days of trial enrolment
Uncontrolled or severe cardiovascular disease (including myocardial infarction within 6 months prior to enrollment
NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease, cardiac amyloidosis, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities)
Other malignancy within the past 5 years prior to enrolment (except for non-active basal cell or non-metastatic squamous cell carcinoma of the skin, cervical carcinoma in situ or Stage 1 carcinoma of the cervix
Known HIV seropositivity or active hepatitis A, B, or C infection
Use of any investigational drug within 30 days prior to enrolment in the trial
Medical or psychiatric condition that could interfere with trial participation
History of hypersensitivity or allergic reaction attributable to compounds containing boron, mannitol or doxorubicin.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen-Ortho Inc. Clinical Trial
Organizational Affiliation
Janssen-Ortho Inc., Canada
Official's Role
Study Director
12. IPD Sharing Statement
Learn more about this trial
A Study Assessing Safety and Effectiveness of BORTEZOMIB Combination Therapy (Bortezomib + Doxorubicin Hydrochloride + Dexamethasone) in Previously Untreated Multiple Myeloma Patients
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