An Efficacy and Safety Study of Bortezomib in Participants Previously Treated for Multiple Myeloma With Limited Kidney Function

Safety and Efficacy of Velcade in Relapsed and/or Refractory Multiple Myeloma Patients With Impaired Renal Function

The purpose of this study is to evaluate the effectiveness and safety of bortezomib in participants previously treated for multiple myeloma (cancer of plasma cells in bone marrow causing numerous tumors and characterized by the presence of abnormal proteins in the blood) with limited kidney function.

Study Overview

• Status: Terminated
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Dexamethasone; Drug: Bortezomib

Detailed Description

This is an open label (all people know the identity of the intervention), multi-center (study conducted at multiple sites), non-comparative, single arm study of bortezomib. The study consists of 3 phases: Screening phase (21 days before Day 1 of cycle 1); Treatment phase (consist of 8 cycles each cycle of 21 days or until disease progression or unacceptable toxicity); and a Follow-up phase (for participants with positive treatment response or stable disease at the final visit). Follow-up for disease progression will be done in every 3 months up to 2 years. Participants who will experience disease progression after completing at least 2 cycles of bortezomib treatment or have no change from baseline in stable disease after completing at least 4 cycles or as per Investigator's discretion will receive dexamethasone. Efficacy will be primarily evaluated by percentage of participants with renal compromised Multiple Myeloma by International Myeloma Working Group (IMWG) uniform response criteria. Participants' safety will be monitored throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Saint John N/A, Canada
  • British Columbia
    • New Westminster, British Columbia, Canada
    • Vancouver, British Columbia, Canada
  • Ontario
    • London, Ontario, Canada
  • Quebec
    • Greenfield Park, Quebec, Canada

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants diagnosed with symptomatic multiple myeloma based on the International Myeloma Working Group (IMWG) criteria; greater than or equal to 10 percent plasma cells in the bone marrow (or tissue biopsy) detected, monoclonal protein in the serum or urine and the, presence of end-organ injury
• Participants with measurable disease defined by at least 1 of the following 5 measurements: a) serum M-protein greater than or equal to 1 gram per deciliter (g/dl), b) Urine M Protein greater than or equal to 200 milligram per 24 hour, c) Serum free light chain (FLC) assay: Involved FLC level greater than 10 mg per dl (mg/dl) provided serum FLC ratio is abnormal, d) Bone marrow plasma cells greater than or equal to 30 percent
• Participants who received at least 1 prior line of chemotherapy for multiple myeloma and, is refractory to or has relapsed after the last therapy
• Participants with Karnofsky performance status greater than 60 or Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Participants with calculated or measured creatinine clearance of less than or equal to 30 mililiter per minute (ml/min). During the screening period, 2 measures of creatinine clearance at least 7 days apart must be obtained, and both must be less than 30 ml/min

Exclusion Criteria:

• Participants who had received bortezomib in previous clinical trial and best response was progressive disease or experienced one or more serious events
• Participants who received nitorsoureas within 6 weeks, or 2 consecutive weeks of intense corticosteroids, or immunotherapy or antibody therapy within 4 weeks before enrolment
• Participants with history of allergic reaction attributable to compounds containing boron or mannitol
• Participants with peripheral neuropathy of Grade 2 or greater intensity at the time of signing informed consent form
• Pregnant or breast-feeding female participants

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Bortezomib and Dexamethasone; Bortezomib 1.3 milligram (mg) per meter^2 (m^2) bolus (a large amount) intravenous (into the vein) injection will be administered once daily on Days 1, 4, 8 and 11 of each 21-day cycle with addition of Dexamethasone 20 mg per day administered orally, once daily on Days 1 and 2, Days 4 and 5, Days 8 and 9 and Days 11 and 12 of each 21-day cycle as per Investigator's discretion for those participants who experience disease progression after treatment completion up to Cycle 2 or have no change from Baseline after completion of at least 4 cycles. The treatment will be given up to 8 cycles (24 weeks).

Drug: Dexamethasone; Dexamethasone 20 mg per day will be administered orally on Days 1 and 2, Days 4 and 5, Days 8 and 9 and Days 11 and 12 of each 21-days cycle as per Investigator's discretion for those participants who experience disease progression after treatment completion up to Cycle 2 or have no change from Baseline after completion of at least 4 cycles. The treatment will be given up to 8 cycles (24 weeks).; Drug: Bortezomib; Bortezomib 1.3 milligram per meter^2 (mg/m^2), bolus intravenous injection will be administered on Days 1, 4, 8 and 11 of each 21-day cycle and up to 8 cycles.; Other Names: Velcade

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Renal Compromised Multiple Myeloma by International Myeloma Working Group (IMWG) Uniform Response Criteria	The IMWG uniform response criteria define; Complete response(CR) as negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow(BM). Stringent CR as CR+normal free light chain ratio and absence of clonal cells in BM Very good partial response (PR) as serum and urine M-protein (monoclonal paraprotein) detectable by immunofixation but not on electrophoresis or 90% or >reduction in serum and urine M-protein level <100 milligram(mg) per 24 hour(hr).PR as <=50% reduction of serum and <= 90% of urine M-protein or up to <200 mg/24 hr.	Week 24 or Early termination visit (30-45 days after last dose)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Response to Treatment	It was assessed by IMWG criteria. It defines complete response as negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow. Very good partial response as serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or > reduction in serum and urine M-protein level<100 mg per 24 hour. Partial Response as <=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by <=90% or to <200mg per 24 hr.	Day 1 of Cycle 1, 2, 3, 4, 5, 5, 6, 7, 8 and Final/Early termination visit (30-45 days after last dose)
Time to Progression (TTP) of Disease	The TTP was defined as the time from the date of starting treatment until the date of first documented evidence of progression of disease or death.	Day 1 (Start of treatment) until the date of first documented evidence of progression of disease or death
Duration of Response	The duration of Response was defined as the time of first recorded achievement of a particular response level, which was defined according to IMWG uniform response criteria, as either complete response, stringent complete response, very good partial response or partial response included only responding participants, until the participants were assessed to have progressive disease.	Day 1 (Start of treatment) until the date of first documented achievement of response
Eastern Cooperative Oncology Group Performance Status (ECOG PS) Score	The ECOG PS Score 0 versus 1, wherein 0 signifies fully active, able to carry all pre-disease performance without restriction and 1 signifies restriction in physically strenuous activity but ambulatory (able to walk) and able to carry out work on a light or sedentary nature.	Day 1 of Cycle 1, 3, 5, 7 and Final visit/Early termination visit (30-45 days after last dose)
Karnofsky Performance Status (KPS) Score	The KPS is used to quantify participant's general well-being and activities of daily life and participants are classified based on their functional impairment. KPS score is 11-level score which ranges between 0 (death) to 100 (no evidence of disease). Higher score means higher ability to perform daily tasks.	Day 1 of Cycle 1, 3, 5, 7 and Final visit (30-45 days after last dose) or early termination visit
Quality of Life Assessment by QLQ C-30	The quality of life was assessed by the questionnaire QLQ C-30 designed by European Organization for the Research and Treatment of Cancer (EORTC). The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer participants. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the fatigue scale is equal to higher level of symptomatology or problems.	Final Visit/Early termination visit (30-45 days after last dose)
Quality of Life Assessed by Euro Quality of Life (EQ-5D)	The EQ-5D is a participant rated questionnaire to assess health-related quality of life in terms of a single utility score. It assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression where 1=better health state (no problems), 3=worst health state. Scoring formula was developed by Euro quality of life group which assigns a utility value for each domain in profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.	Quality of Life (EQ-5D) Final Visit/Early termination visit (30-45 days after last dose)
Renal Function	Renal function was analysed by creatinine clearance. Creatinine clearance was calculated by Cockroft-Gault fourmula. Creatinine clearance is equal to 140 minus age multiplied by weight and constant (1 for men and 0.85 for women) divided by creatinine in (micro mole per liter)	Day 1 of Cycle 1, 2, 3, 4, 5, 5, 6, 7, 8 and Final/Early termination visit (30-45 days after last dose)

Collaborators and Investigators

• Sponsor: Janssen-Ortho Inc., Canada

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: July 17, 2008
• First Submitted That Met QC Criteria: July 17, 2008
• First Posted (Estimate): July 21, 2008

Study Record Updates

• Last Update Posted (Estimate): October 29, 2013
• Last Update Submitted That Met QC Criteria: September 25, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: Multiple Myeloma; Dexamethasone; Bortezomib; Velcade
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone; Bortezomib
• Other Study ID Numbers: CR015082; 26866138MMY2052