Velcade Consolidation Bone Study

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen-Cilag International NV
ClinicalTrials.gov Identifier:
NCT01286077
First received: January 27, 2011
Last updated: April 26, 2016
Last verified: April 2016
  Purpose
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.

Condition Intervention Phase
Multiple Myeloma
Drug: bortezomib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2, Multicentre, Randomised, Open-Label, Parallel Group Study to Evaluate the Effect of VELCADE on Myeloma Related Bone Disease

Resource links provided by NLM:


Further study details as provided by Janssen-Cilag International NV:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Progression Free Survival [ Time Frame: Baseline up to end of study (approximately 4 years 7 months) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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 protein (absolute increase >=200 mg/24 h); or serum/urine M protein unmeasurable: difference between involved and uninvolved free light chain (FLC) levels; absolute increase >10 mg/dL; or % bone marrow plasma cells: absolute value >=10% or definite development of new bone lesions or soft tissue plasmocytomas or definite increase in the size of existing bone lesions or soft tissue plasmocytomas; or development of hypercalcemia attributed solely to the plasma cell proliferative disorder.

  • Tumor Response: Percentage of Participants With Partial Response (PR) Based on International Myeloma Working Group (IMWG) Response Criteria [ Time Frame: Baseline up to end of study (approximately 4 years 7 months) ] [ Designated as safety issue: No ]
    Tumor response was assessed as PR based on IMWG response criteria as >=50% reduction of serum and reduction in 24-h urinary M protein by >=90% or to <200 mg/24 h; or serum/urine M protein unmeasurable:>=50% decrease in the difference between involved and uninvolved FLC levels; or serum/urine M protein and FLC assay unmeasurable: >=50% reduction in plasma cells provided baseline bone marrow plasma cell percentage was >=30%; or plus if present at baseline: >=50% reduction in size of soft tissue plasmocytomas.


Enrollment: 106
Study Start Date: September 2009
Study Completion Date: April 2014
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: bortezomib
bortezomib (Velcade) 1.6 mg/m² bolus injection on Days 1, 8, 15 and 22 every 5 weeks for 4 cycles
Drug: bortezomib
Each cycle will consist of 5 weeks treatment. Subjects in the treatment group will receive: Velcade® 1.6 mg/m2 as an intravenous bolus injection on Days 1, 8, 15, and 22 of each cycle followed by a 13-day rest period (Days 23 to 35) Cycle will be repeated on Day 36. Subjects in the treatment group will receive up to 4 treatment cycles, unless they experience either unacceptable toxicity or if the subject requests to withdraw from the study.
No Intervention: Non-treated control
no treatment, observation only

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01286077

Locations
Austria
Feldkirch N/A, Austria
Graz, Austria
Wien, Austria
Czech Republic
Brno, Czech Republic
Denmark
Vejle, Denmark
Germany
Hamburg, Germany
Kiel, Germany
Mÿnchen, Germany
Greece
Athens, Greece
Sweden
Huddinge, Sweden
Stockholm, Sweden
Turkey
Adana, Turkey
Ankara, Turkey
Antalya, Turkey
Eskisehir, Turkey
Gebse, Turkey
Istanbul, Turkey
Izmir, Turkey
United Kingdom
Edinburgh, United Kingdom
Sheffield Yorks, United Kingdom
Wakefield, United Kingdom
Sponsors and Collaborators
Janssen-Cilag International NV
Investigators
Study Director: Janssen-Cilag International NV Clinical Trial Janssen-Cilag International NV
  More Information

Responsible Party: Janssen-Cilag International NV
ClinicalTrials.gov Identifier: NCT01286077     History of Changes
Other Study ID Numbers: CR016270  26866138MMY2060  2008-004264-39 
Study First Received: January 27, 2011
Results First Received: November 7, 2013
Last Updated: April 26, 2016
Health Authority: Belgium: Ministry of Social Affairs, Public Health and the Environment

Keywords provided by Janssen-Cilag International NV:
Multiple Myeloma
bortezomib
hematology
bone marrow cancer
Myeloma-related bone disease
bone mineral density
bone markers

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Bone Diseases
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Musculoskeletal Diseases
Bortezomib
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 25, 2016