Study of DOXIL/CAELYX (Pegylated Liposomal Doxorubicin) and VELCADE (Bortezomib) or VELCADE Monotherapy for the Treatment of Relapsed Multiple Myeloma

September 28, 2015 updated by: Janssen Research & Development, LLC

A Randomized Controlled Study of DOXIL/CAELYX (Doxorubicin HCL Liposome Injection) and VELCADE (Bortezomib) or VELCADE Monotherapy for the Treatment of Relapsed Multiple Myeloma

The purpose of this study is to evaluate time to progression, overall survival, response rate and safety for the two open-label treatment groups; DOXIL/CAELYX in combination with VELCADE vs. VELCADE monotherapy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a randomized (study drug assigned by chance), parallel-group, open-label (all involved people know the identity of the intervention), multicenter study in 18 countries. A total of 646 patients with multiple myeloma whose disease has progressed after an initial response to at least 1 line of prior therapy or was refractory to initial treatment will be enrolled. The primary endpoint is time to progression (the interval between the date of randomization and the date of disease progression); secondary endpoints are overall survival (the interval between the date of randomization and the patient's death from any cause), response rate (the proportion of patients in the evaluable population who achieved a complete or partial response), and safety. Other study endpoints include patient reported outcomes and exploratory pharmacogenics (to identify genetic markers of response). Patients are assessed for efficacy and safety every 3 weeks until disease progression is documented or for up to 42 weeks from the start of the first dose of study drug. Patients, who do not progress after the 42-week period, are assessed every 6 weeks until disease progression is documented. Efficacy evaluations includes: serum protein electrophoresis, 24-hour urine collection for protein electrophoresis, skeletal survey (plain films), bone marrow biopsy and aspirate, clinical or radiologic assessment of plasmacytomas, and serum calcium. Responses and progressions are assessed objectively by a computer algorithm based on the EBMT criteria. Safety evaluations include adverse event reports, changes in clinical laboratory findings, and tests for cardiac function (multiple gated acquisition scan/echocardiogram and electrocardiogram). Group A: VELCADE monotherapy: VELCADE 1.3 milligram per meter square (mg/m^2) to be administered by i.v. bolus on Days 1, 4, 8, and 11 of each 21-day cycle. Group B: DOXIL/VELCADE combination: treated with VELCADE at the same dose and schedule as specified in Group A. DOXIL/CAELYX 30 mg/m^2 by intravenous infusion given on Day 4 of every 21-day cycle following the administration of VELCADE.

Study Type

Interventional

Enrollment (Actual)

646

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina
      • Ciudad De Buenos Aires, Argentina
      • La Plata, Argentina
      • Mendoza, Argentina
  • Australia
      • Adelaide, Australia
      • Darlinghurst, Australia
      • Melbourne, Australia
      • Perth, Australia
      • Sydney, Australia
  • Austria
      • Graz, Austria
      • Innsbruck, Austria
      • Salzburg, Austria
      • Wels N/A, Austria
      • Wien, Austria
  • Belgium
      • Brussel, Belgium
      • Gent, Belgium
      • Leuven, Belgium
      • Mont-Godinne, Belgium
  • Canada
      • N/a N/a, Canada
      • Quebec, Canada
    • British Columbia
      • Vancouver, British Columbia, Canada
    • Ontario
      • Hamilton, Ontario, Canada
      • Ottawa, Ontario, Canada
    • Quebec
      • Montreal, Quebec, Canada
  • Czech Republic
      • Brno, Czech Republic
      • Olomouc, Czech Republic
      • Praha 2 N/A, Czech Republic
  • France
      • Angers Cedex 1 N/A, France
      • Bobigny, France
      • Creteil N/A, France
      • Lille Cedex N/A, France
      • Nantes N/A, France
      • Pierre Benite, France
      • Toulouse, France
      • Tours, France
      • Vandoeuvre Les Nancy, France
  • Israel
      • Haifa, Israel
      • Jerusalem, Israel
      • Petach Tikva, Israel
      • Ramat Gan, Israel
      • Rehovot, Israel
      • Tel Aviv, Israel
  • Netherlands
      • Amersfoort, Netherlands
      • Amsterdam, Netherlands
      • Amsterdam Zuidoost, Netherlands
      • Delft, Netherlands
      • Den Haag, Netherlands
      • Groningen, Netherlands
      • Nieuwegein, Netherlands
      • Nijmegen, Netherlands
      • Rotterdam, Netherlands
      • Utrecht, Netherlands
  • Poland
      • Bialystok, Poland
      • Gdansk, Poland
      • Lodz, Poland
      • Lublin, Poland
      • Warszawa, Poland
      • Wroclaw, Poland
  • Portugal
      • Coimbra, Portugal
      • Lisboa, Portugal
      • Porto N/A, Portugal
  • Russian Federation
      • Arkhangelsk, Russian Federation
      • Ekaterinburg, Russian Federation
      • Izhevsk, Russian Federation
      • Moscow, Russian Federation
      • Moscow N/A, Russian Federation
      • Nizhny Novgorod, Russian Federation
      • Novosibirsk, Russian Federation
      • Obninsk, Russian Federation
      • St. Petersburg, Russian Federation
  • Singapore
      • Singapore, Singapore
  • South Africa
      • Bloemfontein N/A, South Africa
      • Cape Town, South Africa
      • Johannesburg, South Africa
      • Parktown, South Africa
      • Pretoria Gauteng, South Africa
  • Spain
      • Barcelona, Spain
      • Madrid, Spain
      • Salamanca, Spain
  • United Kingdom
      • Bath, United Kingdom
      • London, United Kingdom
  • United States
    • Alabama
      • Alabaster, Alabama, United States
    • Arizona
      • Surprise, Arizona, United States
    • California
      • Berkeley, California, United States
      • Loma Linda, California, United States
      • Los Angeles, California, United States
      • Sacramento, California, United States
    • Connecticut
      • Norwalk, Connecticut, United States
      • Stamford, Connecticut, United States
    • Florida
      • Jacksonville, Florida, United States
      • Miami, Florida, United States
      • Stuart, Florida, United States
      • West Palm Beach, Florida, United States
    • Georgia
      • Altanta, Georgia, United States
    • Idaho
      • Boise, Idaho, United States
    • Indiana
      • Indianapolis, Indiana, United States
    • Kentucky
      • Lexington, Kentucky, United States
    • Louisiana
      • Metairie, Louisiana, United States
      • New Orleans, Louisiana, United States
    • Minnesota
      • Minneapolis, Minnesota, United States
    • New Jersey
      • Hackensack, New Jersey, United States
    • North Carolina
      • Chapel Hill, North Carolina, United States
      • Charlotte, North Carolina, United States
      • Durham, North Carolina, United States
    • Oregon
      • Portland, Oregon, United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States
      • Pittsburgh, Pennsylvania, United States
    • South Carolina
      • N Charleston, South Carolina, United States
    • Tennessee
      • Nashville, Tennessee, United States

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • Patients with multiple myeloma who have received at least 1 prior therapy and who have either responded and later had progressive disease or have progressed during their first therapy (primary refractory) are eligible for the study
  • Patients who may have received prior doxorubicin but not more than a cumulative dose of 240 milligram per meter square (mg/m^2) doxorubicin, DOXIL, or the equivalent amount of another anthracycline (i.e., 1 mg doxorubicin = 1 mg DOXIL/CAELYX = 1.8 mg epirubicin = 0.3 mg mitoxantrone = 0.25 mg idarubicin)
  • Must have normal cardiac function, as evidenced by a left LVEF within institutional normal limits.

Exclusion Criteria:

  • History of treatment with VELCADE or progressive disease while receiving an anthracycline-containing regimen
  • No change in disease status during initial therapy
  • No treatment for malignancy within past 5 yrs (other than multiple myeloma) or progressive disease while receiving anthracycline-containing regimen
  • Non-secretory disease
  • Myocardial infarct within past 6 months
  • No major surgery in past 30 days.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: VELCADE (bortezomib) monotherapy
Bortezomib (VELCADE) 1.3 milligram per meter square (mg/m^2) by rapid (bolus) i.v. administration given on Days 1, 4, 8, and 11 of each 21-day cycle for up to 8 cycles.
Drug: Bortezomib (VELCADE)
1.3 mg/m^2 by rapid (bolus) i.v. administration given on Days 1, 4, 8, and 11 of each 21-day cycle for up to 8 cycles.
Drug: Bortezomib (VELCADE)
1.3 mg/m^2 by rapid (bolus) i.v. administration given on Days 1, 4, 8, and 11 of each 21-day cycle for up to 8 cycles..
Experimental: DOXIL/CAELYX in combination with VELCADE (bortezomib)
Bortezomib (VELCADE) 1.3 mg/m^2 by rapid (bolus) i.v. administration given on Days 1, 4, 8, and 11 of each 21-day cycle for up to 8 cycles. Doxorubicin hydrochloride (DOXIL/CAELYX) 30 mg/m2 by i.v. infusion will be given on Day 4 of every 21-day cycle after the administration of bortezomib (VELCADE) for up to 8 cycles.
Drug: Bortezomib (VELCADE)
1.3 mg/m^2 by rapid (bolus) i.v. administration given on Days 1, 4, 8, and 11 of each 21-day cycle for up to 8 cycles.
Drug: Bortezomib (VELCADE)
1.3 mg/m^2 by rapid (bolus) i.v. administration given on Days 1, 4, 8, and 11 of each 21-day cycle for up to 8 cycles..
Drug: Doxorubicin hydrochloride (DOXIL/CAELYX)
mg/m^2 by i.v. infusion will be given on Day 4 of every 21-day cycle after the administration of bortezomib (VELCADE) for up to 8 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to Progression (TTP)
Time Frame: Up to 1 year and 4 months (From date of first participant randomization [20 December 2004] up to interim analysis cut-off date [28 April 2006])
Median time to progression of disease is assessed according to International Myeloma Working Group (IMWG) criteria or death from any cause. IMWG criteria: increase of >=25% from lowest level in Serum M-component or (the absolute increase must be >=0.5 gram per deciliter [g/dL]); Urine M component or (the absolute increase must be >=200 milligram per 24 hour. Only in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain levels. The absolute increase >10 mg/dL. Bone marrow plasma cell percentage >=10%. Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing. Development of hypercalcemia. Participants who died or dropped out due to any reason without progression will be censored with the day of death or drop-out, respectively and who are alive at the end of the study without any progression was censored with the last available date.
Up to 1 year and 4 months (From date of first participant randomization [20 December 2004] up to interim analysis cut-off date [28 April 2006])

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: Up to 9 years and 5 months (From date of first participant randomization [20 December 2004] to cut-off date for final survival analysis (16 May 2014)
The OS is defined as the time from the date of first dose of study drug to date of death from any cause. If the participant is alive or the vital status is unknown, the participant will be censored at the date the participant will be last known to be alive.
Up to 9 years and 5 months (From date of first participant randomization [20 December 2004] to cut-off date for final survival analysis (16 May 2014)
Number of Participants With Serious Adverse Events (SAEs)
Time Frame: Up to 1 year and 11 months (From date of first participant randomization [20 December 2004] to cut-off date for safety update (28 November 2006)
A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Up to 1 year and 11 months (From date of first participant randomization [20 December 2004] to cut-off date for safety update (28 November 2006)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Janssen Research & Development, LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2004

Primary Completion (Actual)

May 1, 2014

Study Completion (Actual)

June 1, 2014

Study Registration Dates

First Submitted

February 9, 2005

First Submitted That Met QC Criteria

February 9, 2005

First Posted (Estimate)

February 10, 2005

Study Record Updates

Last Update Posted (Estimate)

October 19, 2015

Last Update Submitted That Met QC Criteria

September 28, 2015

Last Verified

September 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CR004117
  • DOXILMMY3001 (Other Identifier: Janssen Research & Development, LLC)
  • 2004-001842-34 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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