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

NCT ID: NCT00103506

Last Updated: 2015-10-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 646 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-12-31
• Study Completion Date: 2014-06-30

Brief Summary

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.

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.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Bortezomib (VELCADE)

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Bortezomib (VELCADE)

Intervention Type: DRUG

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)

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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..

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC C. Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Alabaster, Alabama, United States

Surprise, Arizona, United States

Berkeley, California, United States

Loma Linda, California, United States

Los Angeles, California, United States

Sacramento, California, United States

Norwalk, Connecticut, United States

Stamford, Connecticut, United States

Jacksonville, Florida, United States

Miami, Florida, United States

Stuart, Florida, United States

West Palm Beach, Florida, United States

Altanta, Georgia, United States

Boise, Idaho, United States

Indianapolis, Indiana, United States

Lexington, Kentucky, United States

Metairie, Louisiana, United States

New Orleans, Louisiana, United States

Minneapolis, Minnesota, United States

Hackensack, New Jersey, United States

Chapel Hill, North Carolina, United States

Charlotte, North Carolina, United States

Durham, North Carolina, United States

Portland, Oregon, United States

Philadelphia, Pennsylvania, United States

Pittsburgh, Pennsylvania, United States

North Charleston, South Carolina, United States

Nashville, Tennessee, United States

Buenos Aires, , Argentina

Ciudad de Buenos Aires, , Argentina

La Plata, , Argentina

Mendoza, , Argentina

Adelaide, , Australia

Darlinghurst, , Australia

Melbourne, , Australia

Perth, , Australia

Sydney, , Australia

Graz, , Austria

Innsbruck, , Austria

Salzburg, , Austria

Vienna, , Austria

Wels, , Austria

Brussels, , Belgium

Ghent, , Belgium

Leuven, , Belgium

Mont-Godinne, , Belgium

Vancouver, British Columbia, Canada

Hamilton, Ontario, Canada

Ottawa, Ontario, Canada

Montreal, Quebec, Canada

Québec, Quebec, Canada

N/a N/a, , Canada

Brno, , Czechia

Olomouc, , Czechia

Praha 2 N/A, , Czechia

Angers Cedex 1 N/A, , France

Bobigny, , France

Créteil, , France

Lille Cedex N/A, , France

Nantes, , France

Pierre-Bénite, , France

Toulouse, , France

Tours, , France

Vandœuvre-lès-Nancy, , France

Haifa, , Israel

Jerusalem, , Israel

Petah Tikva, , Israel

Ramat Gan, , Israel

Rehovot, , Israel

Tel Aviv, , Israel

Amersfoort, , Netherlands

Amsterdam, , Netherlands

Amsterdam-Zuidoost, , Netherlands

Delft, , Netherlands

Groningen, , Netherlands

Nieuwegein, , Netherlands

Nijmegen, , Netherlands

Rotterdam, , Netherlands

The Hague, , Netherlands

Utrecht, , Netherlands

Bialystok, , Poland

Gdansk, , Poland

Lodz, , Poland

Lublin, , Poland

Warsaw, , Poland

Wroclaw, , Poland

Coimbra, , Portugal

Lisbon, , Portugal

Porto, , Portugal

Arkhangelsk, , Russia

Izhevsk, , Russia

Moscow, , Russia

Nizhny Novgorod, , Russia

Novosibirsk, , Russia

Obninsk, , Russia

Saint Petersburg, , Russia

Yekaterinburg, , Russia

Singapore, , Singapore

Bloemfontein, , South Africa

Cape Town, , South Africa

Johannesburg, , South Africa

Parktown, , South Africa

Pretoria Gauteng, , South Africa

Barcelona, , Spain

Madrid, , Spain

Salamanca, , Spain

Bath, , United Kingdom

London, , United Kingdom

Countries

United States; Argentina; Australia; Austria; Belgium; Canada; Czechia; France; Israel; Netherlands; Poland; Portugal; Russia; Singapore; South Africa; Spain; United Kingdom

References

Dimopoulos MA, Orlowski RZ, Facon T, Sonneveld P, Anderson KC, Beksac M, Benboubker L, Roddie H, Potamianou A, Couturier C, Feng H, Ataman O, van de Velde H, Richardson PG. Retrospective matched-pairs analysis of bortezomib plus dexamethasone versus bortezomib monotherapy in relapsed multiple myeloma. Haematologica. 2015 Jan;100(1):100-6. doi: 10.3324/haematol.2014.112037. Epub 2014 Sep 26.

Reference Type: DERIVED

PMID: 25261096 (View on PubMed)

Sonneveld P, Hajek R, Nagler A, Spencer A, Blade J, Robak T, Zhuang SH, Harousseau JL, Orlowski RZ; DOXIL-MMY-3001 Study Investigators. Combined pegylated liposomal doxorubicin and bortezomib is highly effective in patients with recurrent or refractory multiple myeloma who received prior thalidomide/lenalidomide therapy. Cancer. 2008 Apr 1;112(7):1529-37. doi: 10.1002/cncr.23326.

Reference Type: DERIVED

PMID: 18300257 (View on PubMed)

Orlowski RZ, Nagler A, Sonneveld P, Blade J, Hajek R, Spencer A, San Miguel J, Robak T, Dmoszynska A, Horvath N, Spicka I, Sutherland HJ, Suvorov AN, Zhuang SH, Parekh T, Xiu L, Yuan Z, Rackoff W, Harousseau JL. Randomized phase III study of pegylated liposomal doxorubicin plus bortezomib compared with bortezomib alone in relapsed or refractory multiple myeloma: combination therapy improves time to progression. J Clin Oncol. 2007 Sep 1;25(25):3892-901. doi: 10.1200/JCO.2006.10.5460. Epub 2007 Aug 6.

Reference Type: DERIVED

PMID: 17679727 (View on PubMed)

Other Identifiers

DOXILMMY3001

Identifier Type: OTHER

Identifier Source: secondary_id

2004-001842-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR004117

Identifier Type: -

Identifier Source: org_study_id