Clinical Trial: Velcade Consolidation Bone Study

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase 2, Multicentre, Randomised, Open-Label, Parallel Group Study to Evaluate the Effect of VELCADE on Myeloma Related Bone Disease

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 Summary: 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
Sponsor: Janssen-Cilag International NV

Current Primary Outcome:

  • Change From Baseline in Bone Mineral Density (BMD) in the Spine at End of Treatment (EOT) [ Time Frame: 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 ]
    Change from baseline in bone mineral density (BMD) will be assessed by dual energy x-ray absorptiometry scans at baseline and the EOT visit
  • Change From Baseline in Bone Mineral Density (BMD) in the Femur at End of Treatment [ Time Frame: 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 ]
    Change from baseline in bone mineral density (BMD) will be assessed by dual energy x-ray absorptiometry scans at baseline and the end of treatment EOT visit


Original Primary Outcome: Change from baseline in bone mineral density (BMD) assessed by dual energy x-ray absorptometry scans at the end of treatment EOT visit. [ Time Frame: at screening (i.e. between 14 and 1 days prior to start of treatment) and at end of treatment, i.e. 6 weeks after last dose of study treatment, or 24 weeks after randomization (Day 169) ]

Current Secondary Outcome:

  • Progression Free Survival [ Time Frame: Baseline up to end of study (approximately 4 years 7 months) ]
    The Progression-Free Survival (PFS) was assessed as median number of months from baseline until the first documented sign of disease progression (increase in disease; radiographic, clinical, or both) or death due to any cause, whichever occurred earlier.
  • Change From Baseline in Biochemical Bone Markers:Carboxyterminal Telopeptide of Type I Collagen (ICTP), Osteocalcin, Bone-specific Alkaline Phosphatase (BAP) [ Time Frame: Baseline up to end of study (approximately 4 years 7 months) ]
    Bone markers (carboxyterminal telopeptide of type I collagen (ICTP), osteocalcin (Oc) and bone-specific alkaline phosphatase (BAP) was measured on serum samples.
  • Change From Baseline in Biochemical Bone Markers: Carboxyterminal Collagen Crosslinks (CTX-I) [ Time Frame: Baseline up to end of study (approximately 4 years 7 months) ]
    Change from Baseline in Biochemical Bone Markers: CTX-I was assessed
  • Change From Baseline in Biochemical Bone Markers: Dickkopf Homolog 1 (DKK-1) [ Time Frame: Baseline up to end of study (approximately 4 years 7 months) ]
    Bone markers Dickkopf homolog 1 (DKK-1) was measured on serum samples.
  • Number of Patients With Skeletal Events [ Time Frame: Baseline up to end of study (approximately 4 years 7 months) ]
    Number of patients with skeletal-related events (i.e. pathological fracture (vertebral, non-vertebral, combined), radiotherapy, spinal cord compression, orthopaedic surgery, hypercalcaemia) occurring over 24 months study period
  • Appearance of New Bone Lesions Compared to Baseline [ Time Frame: Baseline up to end of study (approximately 4 years 7 months) ]
    Appearance of new bone lesions assessed by skeletal survey compared to baseline
  • Change From Baseline in Spine T-score [ Time Frame: Baseline up to end of study (approximately 4 years 7 months) ]
    T score is used to calculate bone mineral density (calcium and other types of minerals) in an area of the bone. T score is the number of standard deviations above or below the mean for a healthy 30 year old adult of the same sex and ethnicity as a participant. This score is calculated from participant's age, gender and race and skeletal site. T score has a mean of '50' and a standard deviation of '10'. T score lower than its mean indicate low bone mineral density.
  • Karnofsky Performance Status [ Time Frame: Baseline up to end of study (approximately 4 years 7 months) ]
    The Karnofsky performance status is a way to quantify cancer patients' general well-being and activities of daily life and runs from 100 to 0, where 100 is "perfect" health and 0 is death.
  • Overall Survival [ Time Frame: Baseline up to end of study (approximately 4 years 7 months) ]
    Overall survival defined as time from first treatment of MMY, i.e. day of first dose of induction therapy for MMY to date of death
  • Change From Baseline in Quality of Life Assessed by Euro Quality of Life (EQ-5D) [ Time Frame: Baseline up to end of study (approximately 4 years 7 months) ]
    Subjects were asked to rate their general state of health on a Visual analog scale (in millimeter [mm]) ranging from 0 (worst state of health) to 100 (best conceivable state of health) mm.
  • 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 [ Time Frame: Baseline up to end of study (approximately 4 years 7 months) ]
    Tumor response was assessed as VGPR based on IMWG response criteria if, a) serum/urine M protein detectable by immunofixation but not on electrophoresis or; b) greater than or equal to 90% reduction in serum M protein plus urine M protein level less than 100 milligram/24 hour. CR=normal free light chain (FLC) ratio and absence of phenotypically aberrant plasma cells (PC) in bone marrow with a minimum of 3000 total PC analyzed by multiparametric flow cytometry; Complete response (CR) negative immunofixation on the serum and urine and, disappearance of any soft tissue plasmocytomas and <5% plasma cells in bone marrow.
  • Tumor Response: Percentage of Participants With Stable Disease (SD) or Progressive Disease (PD) Based on International Myeloma Working Group (IMWG) Response Criteria [ Time Frame: Baseline up to end of study (approximately 4 years 7 months) ]
    Tumor response was assessed as SD based on IMWG response criteria as not meeting criteria for CR, VGPR, PR, or progressive disease; PD as Increase of >=25% from lowest response level in any one or more of the following: serum M protein (absolute increase >=0.5 g/dl)c or urine M protei

    Original Secondary Outcome:

    • change in BMD over time and biochemical markers [ Time Frame: baseline, the 1st day of cycle 3 or day 71, EOT visit (i.e. 6 weeks after last dose of study treatment, or 24 weeks after randomization (Day 169)) , Month 4-6-12-18 after EOT ]
    • Progression Free Survival [ Time Frame: At each visit (10 to 22 visits in total) from screening to 18 months after end of treatment (approximately 24 months after randomization) ]
    • skeletal events and appearance of new bone lesions [ Time Frame: EOT (i.e. 6 weeks after last dose of study treatment, or 24 weeks after randomization (Day 169)), month 18 after EOT ]


    Information By: Janssen-Cilag International NV

    Dates:
    Date Received: January 27, 2011
    Date Started: September 2009
    Date Completion:
    Last Updated: April 26, 2016
    Last Verified: April 2016