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

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

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.

Study Overview

• Status: Completed
• Conditions: Amyloidosis
• Intervention / Treatment: Drug: VELCADE

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90049
      • Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Center - Emory Clinic School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
  • New York
    • New York, New York, United States, 10017
      • MSKCC

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:

1. Male or Female 18 y/o and older
2. Female patients must be practicing an effective method of birth control
3. Biopsy-proven AL-amyloidosis
4. Must have been previously treated (failed at least 1 previous treatment) and in the opinion of the physician, patient requires further treatment

Exclusion Criteria:

1. Hypersensitivity to boron or mannitol
2. Prior treatment with VELCADE
3. Patient requires other concomitant chemotherapy, radiotherapy or ancillary therapy considered investigational
4. Uncontrolled infection

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; VELCADE	Drug: VELCADE; 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; Other Names: Bortezomib

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Millennium Pharmaceuticals, Inc.
• Collaborators: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: June 1, 2005
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): September 1, 2009

Study Registration Dates

• First Submitted: March 1, 2006
• First Submitted That Met QC Criteria: March 2, 2006
• First Posted (Estimate): March 3, 2006

Study Record Updates

• Last Update Posted (Estimate): June 25, 2012
• Last Update Submitted That Met QC Criteria: June 19, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Proteostasis Deficiencies; Amyloidosis; Antineoplastic Agents; Bortezomib
• Other Study ID Numbers: 26866138-CAN-2007