Open-Label Phase 1/2 Study of VELCADE for Injection in Patients With Light-chain (AL)-Amyloidosis

Study Overview
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Brief Summary
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This is a phase 1/2 open-label, dose-escalation study investigating single-agent therapy with VELCADE in patients with previously treated systemic AL-amyloidosis who require further treatment.

Official Title
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An Open-Label Phase 1/2 Study of VELCADE for Injection in Subjects With Light-Chain (AL)-Amyloidosis

Conditions
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Amyloidosis

Intervention / Treatment
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* Drug: VELCADE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or Female 18 y/o and older Female patients must be practicing an effective method of birth control Biopsy-proven AL-amyloidosis Must have been previously treated (failed at least 1 previous treatment) and in the opinion of the physician, patient requires further treatment Exclusion Criteria: Hypersensitivity to boron or mannitol Prior treatment with VELCADE Patient requires other concomitant chemotherapy, radiotherapy or ancillary therapy considered investigational Uncontrolled infection

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>VELCADE | Drug: VELCADE<br>* Once weekly at: 0.7, 1.0, 1.3 or 1.6 mg/m2 Or Twice-weekly at: 0.7, 1.0, or 1.3 mg/m2<br>* Other names: Bortezomib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose | Maximum Tolerated Dose (MTD) was defined as the highest dose level that has 0/1 out of 6 patients experiences Dose Limited Toxicity (DLT). MTD is defined separately for QW and BIQ dose cohorts. DLT was defined as adverse events occurring during Cycle 1 and: (1) related to VELCADE, (2) Grade 4 thrombocytopenia or neutropenia, (3) Grade 3 or higher nonhematologic toxicity. | 5 weeks in once weekly (QW) dose cohorts and 3 weeks in twice weekly (BIW) dose cohorts | 
| Subjects With Treatment Emergent Adverse Events | Treatment emergent adverse events observed during outcome measure time frame | from first study-related procedure to 30 days after last dose of study medication | 
| Subjects With Serious Treatment Emergent Adverse Events | Serious treatment emergent adverse events observed during outcome measure time frame | from first study-related procedure to 30 days after last dose of study medication | 
| Subjects Grade 3/4/5 Treatment Emergent Adverse Events | Grade 3/4/5 treatment emergent adverse events observed during outcome measure time frame. Grade is determined according to Common Terminology Criteria for Adverse Event (CTCAE) Version 3.0. | from first study-related procedure to 30 days after last dose of study medication | 
| Subjects With Treatment Emergent Adverse Events Leading to Treatment Termination | Treatment emergent adverse events observed during outcome measure time frame leading to treatment termination | from first study-related procedure to 30 days after last dose of study medication | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Confirmed Hematologic Responders | Hematologic response was determined by the investigator per the response criteria for immunoglobulin light chain amyloidosis by Gertz (2005). It include Complete and Partial Responders (CR+PR). CR requires serum and urine negative for a monoclonal protein by immunofixation and free light chain ratio normal. PR requires: 1. reduction in quantitative serum M-protein by 50% if baseline value is at least 0.5 g/dL, 2. if light chain is detected in the urine (with a consistent peak and >100 mg/ 24 hours), then 50% reduction is required, 3. if free light chain >10 mg/dL, reduction by 50% is required. | from first dose of study medication to end of study visit |