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

Primary Purpose

Amyloidosis

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
VELCADE
Sponsored by
Millennium Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Amyloidosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute
  • Winship Cancer Center - Emory Clinic School of Medicine
  • Boston Medical Center
  • MSKCC

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

1

Arm Description

VELCADE

Outcomes

Primary Outcome Measures

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.
Subjects With Treatment Emergent Adverse Events
Treatment emergent adverse events observed during outcome measure time frame
Subjects With Serious Treatment Emergent Adverse Events
Serious treatment emergent adverse events observed during outcome measure time frame
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.
Subjects With Treatment Emergent Adverse Events Leading to Treatment Termination
Treatment emergent adverse events observed during outcome measure time frame leading to treatment termination

Secondary Outcome Measures

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.

Full Information

First Posted
March 1, 2006
Last Updated
June 19, 2012
Sponsor
Millennium Pharmaceuticals, Inc.
Collaborators
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
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1. Study Identification

Unique Protocol Identification Number
NCT00298766
Brief Title
Open-Label Phase 1/2 Study of VELCADE for Injection in Patients With Light-chain (AL)-Amyloidosis
Official Title
An Open-Label Phase 1/2 Study of VELCADE for Injection in Subjects With Light-Chain (AL)-Amyloidosis
Study Type
Interventional

2. Study Status

Record Verification Date
June 2012
Overall Recruitment Status
Completed
Study Start Date
June 2005 (undefined)
Primary Completion Date
July 2009 (Actual)
Study Completion Date
September 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Millennium Pharmaceuticals, Inc.
Collaborators
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

4. Oversight

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Amyloidosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
70 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
VELCADE
Intervention Type
Drug
Intervention Name(s)
VELCADE
Other Intervention Name(s)
Bortezomib
Intervention Description
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
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose
Description
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.
Time Frame
5 weeks in once weekly (QW) dose cohorts and 3 weeks in twice weekly (BIW) dose cohorts
Title
Subjects With Treatment Emergent Adverse Events
Description
Treatment emergent adverse events observed during outcome measure time frame
Time Frame
from first study-related procedure to 30 days after last dose of study medication
Title
Subjects With Serious Treatment Emergent Adverse Events
Description
Serious treatment emergent adverse events observed during outcome measure time frame
Time Frame
from first study-related procedure to 30 days after last dose of study medication
Title
Subjects Grade 3/4/5 Treatment Emergent Adverse Events
Description
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.
Time Frame
from first study-related procedure to 30 days after last dose of study medication
Title
Subjects With Treatment Emergent Adverse Events Leading to Treatment Termination
Description
Treatment emergent adverse events observed during outcome measure time frame leading to treatment termination
Time Frame
from first study-related procedure to 30 days after last dose of study medication
Secondary Outcome Measure Information:
Title
Best Confirmed Hematologic Responders
Description
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.
Time Frame
from first dose of study medication to end of study visit

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor
Organizational Affiliation
Millennium Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute
City
Los Angeles
State/Province
California
ZIP/Postal Code
90049
Country
United States
Facility Name
Winship Cancer Center - Emory Clinic School of Medicine
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Boston Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
MSKCC
City
New York
State/Province
New York
ZIP/Postal Code
10017
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
25202139
Citation
Reece DE, Hegenbart U, Sanchorawala V, Merlini G, Palladini G, Blade J, Fermand JP, Hassoun H, Heffner L, Kukreti V, Vescio RA, Pei L, Enny C, Esseltine DL, van de Velde H, Cakana A, Comenzo RL. Long-term follow-up from a phase 1/2 study of single-agent bortezomib in relapsed systemic AL amyloidosis. Blood. 2014 Oct 16;124(16):2498-506. doi: 10.1182/blood-2014-04-568329. Epub 2014 Sep 8.
Results Reference
derived
PubMed Identifier
21562045
Citation
Reece DE, Hegenbart U, Sanchorawala V, Merlini G, Palladini G, Blade J, Fermand JP, Hassoun H, Heffner L, Vescio RA, Liu K, Enny C, Esseltine DL, van de Velde H, Cakana A, Comenzo RL. Efficacy and safety of once-weekly and twice-weekly bortezomib in patients with relapsed systemic AL amyloidosis: results of a phase 1/2 study. Blood. 2011 Jul 28;118(4):865-73. doi: 10.1182/blood-2011-02-334227. Epub 2011 May 11.
Results Reference
derived
PubMed Identifier
19498019
Citation
Reece DE, Sanchorawala V, Hegenbart U, Merlini G, Palladini G, Fermand JP, Vescio RA, Liu X, Elsayed YA, Cakana A, Comenzo RL; VELCADE CAN2007 Study Group. Weekly and twice-weekly bortezomib in patients with systemic AL amyloidosis: results of a phase 1 dose-escalation study. Blood. 2009 Aug 20;114(8):1489-97. doi: 10.1182/blood-2009-02-203398. Epub 2009 Jun 4.
Results Reference
derived

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

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