Clinical trial NCT01286077: Velcade Consolidation Bone Study
Official title: A Phase 2, Multicentre, Randomised, Open-Label, Parallel Group Study to Evaluate the Effect of VELCADE on Myeloma Related Bone Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
bortezomib
hematology
bone marrow cancer
Myeloma-related bone disease
bone mineral density
bone markers
Lead sponsor: Janssen-Cilag International NV
Sponsor class: INDUSTRY
First posted: 2011-01-31
Enrollment: 106
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the effect of bortezomib on myeloma-related bone disease, analyzing bone mineral density (BMD) in patients with Multiple Myeloma (MMY) who have received high dose chemotherapy and autologous stem cell transplantation for primary treatment of MMY (single- or double-transplant). Eligible patients will be randomized (study treatment assigned by chance like flipping a coin) to either bortezomib or observation alone. Patients in the bortezomib arm will receive treatment of bortezomib for a total of 4 cycles. All subjects will be followed for a total of 24 months after randomization.

Detailed description: This is a randomized, open-label (all people involved know the identity of the intervention), multicenter, multi-country parallel group study (each group of patients will be treated at the same time) in patients with Multiple Myeloma (MMY) who have received high dose chemotherapy and autologous stem cell transplantation for primary treatment of MMY (single- or double-transplant). The purpose of the study is to assess the effect of bortezomib on myeloma-related bone disease by analyzing bone mineral density. Approximately 80% of patients with MMY may experience myeloma-related bone disease. Myeloma-related bone disease may cause skeletal complications, including bone pain, bone lesions, abnormal fractures and super-elevated calcium concentrations in the blood. This study is investigating the safety and efficacy of an experimental drug, bortezomib, to consolidate the response to the primary treatment compared to no such consolidation treatment. The analyses in this study will be exploratory in nature, since the study will not address any pre-defined statements but is designed to generate valid hypotheses on safety and efficacy issues. Bortezomib is currently marketed for the treatment of different types of cancer including MMY. Bortezomib has been shown to promote bone formation and increase the number of bone-regenerating cells in preliminary studies. In the present study, the effect of bortezomib on bone formation will be assessed by dual energy x-ray absorptiometry (DXA) measuring bone mineral density, which is a measure for the quality of the bone structures. Several bone markers will be measured on serum samples. Bone markers are indicators of the bone activity. Patients will be evaluated for eligibility within a 14-day screening period, after providing written informed consent. Eligible patients will then be randomised to either bortezomib or observation alone. Baseline efficacy and safety assessments should be available on Cycle 1 Day 1 prior to administration of study medication. Randomization will be stratified by bisphosphonate treatment (use or not) at baseline and age (65 years or more versus less than 65 years). The treatment period is defined as the time the patient is actively receiving study treatment. Patients in the bortezomib arm will receive treatment of bortezomib for a total of 4 cycles or until start of alternative MMY treatment if earlier. Each cycle will consist of 5 weeks treatment. Subjects in the treatment group will receive bortezomib 1.6 mg/m2 on Days 1, 8, 15, and 22 of each cycle followed by a 13-day rest period (Days 23 to 35). Bisphosphonate therapy can be administered as medically indicated and according to local practice. Patients are to attend study center visits on Days 1, 8, 15, and 22 of each treatment cycle or at Days 1, 36, 71, and 106 in the observation arm and at end of treatment (EOT) Visit. During these visits, different evaluations will be conducted to follow treatment safety: symptom directed physical examination, vital signs and laboratory tests. In addition, at Day 1 of Cycle 3 (prior to dosing) or Day 71 in the observation arm, patients will be assessed for disease progression or relapse by measurements of M-protein in serum and urine. If needed, absence of M-protein in serum and urine will be confirmed by immunofixation. Additional evaluations may be performed to document patient's clinical status and ability to tolerate additional therapy as clinically indicated. All patients will be followed for a total of 24 months since baseline. After end of the treatment phase, there will be a long-term follow-up period with visits at 4, 6, 12 and 18 months after the EOT Visit. In case the patient started alternative MMY treatment before completing the 18 months of follow-up, study assessments will stop, except for QoL assessments, which are to be continued up to 18 months of follow-up, and for a long-term follow-up for survival, which will be collected every 6 months by either a telephone call or a visit to the study site. The follow-up for survival will continue for all patients until the last patient has completed follow-up. In addition to scheduled visits, patients may have additional visits as clinically indicated. Every patient who was randomized should enter the long-term follow-up phase. Assessment of progressive disease (PD) or relapse from complete response (CR) should be performed according to the International Myeloma Working Group (IMWG) 2009 criteria. Changes in serum and urine M-protein (monoclonal paraprotein) levels will be confirmed by immunofixation in patients without measurable serum and urine M-protein levels. Karnofsky performance status will also be assessed. Safety will be assessed by monitoring of adverse events, physical examination (including neurological/peripheral neurological examinations), vital signs measurements and clinical laboratory tests. A total of two exploratory analyses will be performed for the present study: The first analysis (main analysis) will be presented after completion of the EOT Visit (24-weeks data). The second analysis will be the analysis at the end of the study on 18 months follow-up data. Patients in the bortezomib arm will receive treatment of bortezomib 1.6 mg/m² as a bolus infusion on Days 1, 8, 15, and 22 every 5 weeks for a total of 4 cycles

Eligibility criteria: Inclusion Criteria:

* Adult Multiple Myeloma patients in partial response or better after high dose chemotherapy and autologous stem cell transplantation
* Patient fulfills defined laboratory requirements within 14 days before enrolment
* If female, is either postmenopausal for more than 24 consecutive months or surgically sterilized or willing to use an acceptable method of birth control for defined period
* If male, agree to use an acceptable barrier method of contraception and to not donate sperm up to 3 months following treatment

Exclusion Criteria:

* Patient received another antimyeloma or experimental therapy following autologous stem cell transplantation
* Patient has a peripheral neuropathy or neuropathic pain of grade 2 or greater intensity as defined by the NCI common terminology criteria of adverse event (NCI CTCAE) version 3.0
* Patient has an uncontrolled or severe cardiovascular disease within 6 months of enrolment
* Patient has any conditions that would compromise his/her well-being or the completion of the study requirements

Primary outcomes:
measure: Change From Baseline in Bone Mineral Density (BMD) in the Spine at End of Treatment (EOT)
timeFrame: at screening (i.e. between 14 and 1 days prior to start of treatment) and at end of treatment (EOT), i.e. 24 weeks after randomization or until start of alternative MMY therapy, if earlier
measure: Change From Baseline in Bone Mineral Density (BMD) in the Femur at End of Treatment
timeFrame: at screening (i.e. between 14 and 1 days prior to start of treatment) and at end of treatment (EOT), i.e. 24 weeks after randomization or until start of alternative MMY therapy, if earlier
Secondary outcomes:
measure: Progression Free Survival
timeFrame: Baseline up to end of study (approximately 4 years 7 months)
measure: Change From Baseline in Biochemical Bone Markers:Carboxyterminal Telopeptide of Type I Collagen (ICTP), Osteocalcin, Bone-specific Alkaline Phosphatase (BAP)
timeFrame: Baseline up to end of study (approximately 4 years 7 months)
measure: Change From Baseline in Biochemical Bone Markers: Carboxyterminal Collagen Crosslinks (CTX-I)
timeFrame: Baseline up to end of study (approximately 4 years 7 months)
measure: Change From Baseline in Biochemical Bone Markers: Dickkopf Homolog 1 (DKK-1)
timeFrame: Baseline up to end of study (approximately 4 years 7 months)
measure: Number of Patients With Skeletal Events
timeFrame: Baseline up to end of study (approximately 4 years 7 months)
measure: Appearance of New Bone Lesions Compared to Baseline
timeFrame: Baseline up to end of study (approximately 4 years 7 months)
measure: Change From Baseline in Spine T-score
timeFrame: Baseline up to end of study (approximately 4 years 7 months)
measure: Karnofsky Performance Status
timeFrame: Baseline up to end of study (approximately 4 years 7 months)
measure: Overall Survival
timeFrame: Baseline up to end of study (approximately 4 years 7 months)
measure: Change From Baseline in Quality of Life Assessed by Euro Quality of Life (EQ-5D)
timeFrame: Baseline up to end of study (approximately 4 years 7 months)
measure: Tumor Response: Percentage of Participants With Very Good Partial Response (VGPR) or Stringent Complete Response (sCR) or Complete Response (CR) Based on International Myeloma Working Group (IMWG) Response Criteria
timeFrame: Baseline up to end of study (approximately 4 years 7 months)
measure: Tumor Response: Percentage of Participants With Stable Disease (SD) or Progressive Disease (PD) Based on International Myeloma Working Group (IMWG) Response Criteria
timeFrame: Baseline up to end of study (approximately 4 years 7 months)
measure: Tumor Response: Percentage of Participants With Partial Response (PR) Based on International Myeloma Working Group (IMWG) Response Criteria
timeFrame: Baseline up to end of study (approximately 4 years 7 months)
Other outcomes:
Locations:
city: Feldkirch N/A
country: Austria
city: Graz
country: Austria
city: Wien
country: Austria
city: Brno
country: Czech Republic
city: Vejle
country: Denmark
city: Hamburg
country: Germany
city: Kiel
country: Germany
city: Mÿnchen
country: Germany
city: Athens
country: Greece
city: Huddinge
country: Sweden
city: Stockholm
country: Sweden
city: Adana
country: Turkey
city: Ankara
country: Turkey
city: Antalya
country: Turkey
city: Eskisehir
country: Turkey
city: Gebse
country: Turkey
city: Istanbul
country: Turkey
city: Izmir
country: Turkey
city: Edinburgh
country: United Kingdom
city: Sheffield Yorks
country: United Kingdom
city: Wakefield
country: United Kingdom
Study officials:
affiliation: Janssen-Cilag International NV
name: Janssen-Cilag International NV Clinical Trial
role: STUDY_DIRECTOR
References: