Clinical trial NCT00431769: An Efficacy and Safety Study of Bortezomib Re-treatment in Multiple Myeloma
Official title: A Phase II, Open-Label Trial Using Velcade for ReTreatment of Multiple Myeloma Subjects Following an Initial Response to Velcade
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: Multiple myeloma
Bortezomib
Dexamethasone
VELCADE
Lead sponsor: Janssen-Cilag International NV
Sponsor class: INDUSTRY
First posted: 2007-02-06
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and efficacy of bortezomib in participants with multiple myeloma who have previously responded to a bortezomib based therapy.

Detailed description: This is an Open-Label (all people know the identity of the intervention), non-randomized, multicenter (when more than one hospital or medical school team work on a medical research study), single arm study to evaluate the safety and efficacy of bortezomib in participants with multiple myeloma (cancer of the types of cells normally found in bone marrow) who have previously responded to a bortezomib based therapy. Participants will be non-randomly assigned to single group bortezomib. Participants will be treated with bortezomib alone or in combination with another drug (dexamethasone). Bortezomib will be given intravenously (i.v. \[into a vein\]) twice Weekly, on Days 1, 4, 8 and 11 of each cycle followed by a 10-day (Days 12 to 21) rest period. The total duration of treatment period will be 8 cycles, each lasting 3 weeks. The initial bortezomib dose is the last tolerated dose (1.0 or 1.3 milligram per metersquare \[mg/ m\^2\] on the previous bortezomib-based treatment. Participants who start the study on a dose of 1.0 mg/m\^2 bortezomib and tolerate the dose well could have their dose escalated to 1.3 mg/m\^2. Doses above 1.3 mg/m\^2 are not allowed. A complete cycle comprises 4 doses of bortezomib. Dexamethasone will be first introduced in Cycles 1 to 5 (i.e.dexamethasone will not be introduced for the first time in Cycles 6 to 8). The median total dose of dexamethasone received per cycle ranges from 120 mg (cycle 7) to 160 mg (cycles 1 to 6 and 8). Efficacy will be primarily assessed by determining Best Confirmed Response according to the European Group for Blood and Marrow Transplantation (EBMT) criteria. Participant's safety will be monitored throughout the study.

Eligibility criteria: Inclusion Criteria:

* Participant was previously diagnosed with multiple myeloma based on standard criteria and had measurable disease. Measurable disease for secretory multiple myeloma was defined as any quantifiable serum M-protein value (generally, but not exclusively, greater than (\>) 1 gram per deciliter (g/dL) immunoglobulin (Ig) G Myeloma protein (M-protein) and \>0.5 g/dL Ig A) or urine light-chain excretion of equal to (=) or \>200 milligram (mg)/24 hour
* Participant previously tolerated 1.0 or 1.3 mg/metersquare (m\^2) bortezomib alone or in combination with other agents and had complete response (CR) or partial response (PR) upon completion of bortezomib therapy
* It had been greater than or equal to (\>=) 6 months since the participant's last bortezomibdose and the participant had progressive disease (PD) if prior response to bortezomib was PR or the participant had relapsed from CR
* Participant had a life expectancy \>3 months
* If female, the participant was either postmenopausal or surgically sterilized or willing to use an acceptable method of birth control from screening through at least 30 days after completion of the last cycle

Exclusion Criteria:

* Participant had received chemotherapy, radiotherapy, antibody, immunotherapy, or experimental therapy to treat multiple myeloma since their last dose of bortezomib. Note: participants could have received localized palliative radiotherapy for complications due to osteolytic bone lesions. Participants could have received steroids (dexamethasone or equivalent) or thalidomide or interferon as maintenance therapy since their last dose of bortezomib according to local standard of care. In addition, participants could have received a cumulative dose of up to 160 mg dexamethasone or equivalent as emergency therapy within 4 weeks prior to enrolment. Participants could have received high dose therapy/stem cell transplantation after induction regimen containing bortezomib, but only if PR or CR was observed during bortezomib containing induction therapy
* Participant had uncontrolled or severe cardiovascular disease, including myocardial infarction within 6 months of enrolment or had New York Heart Association Class III or IV heart failure, uncontrolled angina, clinically significant pericardial disease, severe uncontrolled ventricular arrhythmias or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
* Participant had poorly controlled hypertension, diabetes mellitus, or other serious medical or psychiatric illness that could potentially interfere with the completion of treatment according to the protocol
* Participant had another malignancy within the past 5 years. Exceptions were made for the following if they were treated and not active: basal cell or non-metastatic squamous cell carcinoma of the skin, cervical carcinoma in situ or International Federation of Gynecology and Obstetrics Stage 1 carcinoma of the cervix
* Patient has an uncontrolled or severe cardiovascular disease, within 6 months of enrolment
* Female participant was pregnant or breast feeding. Confirmation that the participant was not pregnant was to be established by a negative beta human chorionic gonadotropin pregnancy test result obtained during the Screening period. Pregnancy testing was not required for post menopausal or surgically sterilized women.

Primary outcomes:
measure: Best Confirmed Response to Bortezomib Re-Treatment
timeFrame: Day 1 of every alternate cycle starting from Cycle 1 up to End of Treatment (30 to 42 days after last dose administration of bortezomib)
Secondary outcomes:
measure: Participants With Percent Change in Baseline Serum Monoclonal Protein (M-protein) Best Confirmed Response Category
timeFrame: Day 1 of every alternate cycle starting from Cycle 1 up to End of Treatment (30 to 42 days after last dose administration of bortezomib)
measure: Participants with Percent Change in Baseline Urine Monoclonal Protein (M-protein) Best Confirmed Response Category
timeFrame: Day 1 of every alternate cycle starting from Cycle 1 up to End of Treatment (30 to 42 days after last dose administration of bortezomib)
measure: Duration of Best Confirmed Response (DOR)
timeFrame: Day 1 Cycle 1 up to last follow-up visit (8 weeks until PD)
measure: Time to Progression (TTP) for Best Confirmed Response
timeFrame: (Day 1 Cycle 1 up to last follow-up visit date (8 weeks until PD)
Other outcomes:
Locations:
city: Graz
country: Austria
city: Oberpullendorf
country: Austria
city: Wien
country: Austria
city: Antwerpen
country: Belgium
city: Brussels
country: Belgium
city: Brussel
country: Belgium
city: Gent
country: Belgium
city: Roeselare
country: Belgium
city: Dijon
country: France
city: Limousis
country: France
city: Marseille
country: France
city: Nantes
country: France
city: Paris
country: France
city: Pessac
country: France
city: Bad Soden
country: Germany
city: Berlin
country: Germany
city: Erlangen
country: Germany
city: Hamburg
country: Germany
city: Hamm
country: Germany
city: Hannover
country: Germany
city: Kiel
country: Germany
city: Köln
country: Germany
city: Mainz
country: Germany
city: Würselen
country: Germany
city: Athens
country: Greece
city: Patra
country: Greece
city: Thessalonikis
country: Greece
city: Luxembourg
country: Luxembourg
city: Almada N/A
country: Portugal
city: Coimbra
country: Portugal
city: Lisboa
country: Portugal
city: Barcelona
country: Spain
city: Cadiz N/A
country: Spain
city: Málaga
country: Spain
city: Salamanca
country: Spain
city: Santiago De Compostela
country: Spain
city: Sevilla
country: Spain
city: Toledo
country: Spain
city: Zaragoza
country: Spain
Study officials:
affiliation: Janssen-Cilag International NV
name: Janssen-Cilag International NV Clinical Trial
role: STUDY_DIRECTOR
References: