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

Phase 2TerminatedNCT00718640

Janssen-Ortho Inc., Canada10 enrolled

Overview

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.

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

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Multiple Myeloma

Interventions

DexamethasoneDRUG

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).

BortezomibDRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (5)

Unnamed facility

New Westminster, British Columbia, Canada

Unnamed facility

Vancouver, British Columbia, Canada

Unnamed facility

London, Ontario, Canada

Unnamed facility

Greenfield Park, Quebec, Canada

Unnamed facility

Saint John, Canada

Outcomes

Primary Outcomes

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.

Time frame: Week 24 or Early termination visit (30-45 days after last dose)

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.