Clinical trial NCT00103506: Study of DOXIL/CAELYX (Pegylated Liposomal Doxorubicin) and VELCADE (Bortezomib) or VELCADE Monotherapy for the Treatment of Relapsed Multiple Myeloma
Official title: A Randomized Controlled Study of DOXIL/CAELYX (Doxorubicin HCL Liposome Injection) and VELCADE (Bortezomib) or VELCADE Monotherapy for the Treatment of Relapsed Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
Doxil
Caelyx
Doxorubicin
Velcade
Bortezomib
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2005-02-10
Enrollment: 646
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

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