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: May 21, 2014
Last verified: May 2014
  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: until 18 months after end of treatment (approximately 24 months after randomization) ] [ Designated as safety issue: No ]
    Progression-free survival (PFS) defined as time from first treatment of MMY, i.e. day of first dose of induction therapy for MMY, to Progressive Disease, relapse from Complete Response, or death

  • Change From Baseline in Biochemical Bone Markers [ Time Frame: baseline, Day 1 of cycle 3, EOT visit (24 weeks after randomization or until start of alternative MMY therapy, if earlier) and 4, 6, 12 and 18 months after EOT ] [ Designated as safety issue: No ]
    Bone markers (carboxyterminal telopeptide of type I collagen (ICTP), carboxyterminal collagen crosslinks (CTX-I), osteocalcin (Oc), bone-specific alkaline phosphatase (BAP) and Dickkopf homolog 1 (DKK-1)) will be measured on serum samples.

  • Skeletal Events [ Time Frame: At each visit from screening to 18 months after EOT (approximately 24 months after randomization) ] [ 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: at screening, EOT (24 weeks after randomization or until start of alternative MMY therapy, if earlier) and 18 months after EOT ] [ Designated as safety issue: No ]
    Appearance of new bone lesions assessed by skeletal survey compared to baseline

  • Change From Baseline in BMD Over Time [ Time Frame: at Day 1 of Cycle 3 or Day 71 in the observation arm, and and 6, 12 and 18 months after EOT ] [ Designated as safety issue: No ]
    Change from baseline in BMD will be assessed by dual energy x-ray absorptiometry scans

  • Karnofsky Performance Status [ Time Frame: at screening, Day 1 of Cycle 2, 3, and 4 or Day 36, 71 and 106 for observation arm, at EOT Visit, and and 4, 6, 12 and 18 months after EOT or start of alternative MMY therapy, if earlier ] [ 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: until 18 months after EOT (approximately 24 months after randomization) ] [ 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


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

  Hide Detailed Description

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

Ages Eligible for Study:   18 Years and older
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

No publications provided

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: May 21, 2014
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:
Bone Diseases
Multiple Myeloma
Neoplasms, Plasma Cell
Musculoskeletal 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
Bortezomib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 31, 2014