Clinical trial NCT00056160: CC-5013 Plus Dexamethasone Versus Dexamethasone Alone in Previously Treated Subjects With Multiple Myeloma
Official title: A Multicenter, Randomized, Parallel-Group, Double-blind, Placebo-controlled Study of CC-5013 Plus Dexamethasone Versus Dexamethasone Alone in Previously Treated Subjects With Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
Refractory and Relapsed
Revlimid
CC5013
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2003-03-07
Enrollment: 353
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: Randomized subjects will receive CC-5013 plus high-dose dexamethasone or placebo appearing identical to CC-5013 plus high-dose dexamethasone in 4-week cycles. Each subject will participate in a treatment phase and a follow-up phase.

Detailed description: This was a phase 3, multicenter, double-blind, placebo-controlled, parallel-group study of the efficacy and safety of CC-5013 plus oral pulse high-dose dexamethasone and oral pulse high-dose dexamethasone therapy alone in subjects with relapsed or refractory multiple myeloma. Eligible subjects were randomized in a 1:1 ratio to 1 of 2 treatment groups: Subjects in the CC-5013/Dex treatment group took 25 mg of CC-5013 orally once daily on Days 1 to 21 and a matching placebo capsule once daily on Days 22 to 28 of each 28-day cycle; Subjects in the Placebo/Dex treatment group took 1 placebo capsule on Days 1 to 28 of each 28-day cycle. Subjects in both treatment groups took 40 mg of dexamethasone orally once daily on Days 1 to 4, 9 to 12, and 17 to 20 of each 28-day cycle for the first 4 cycles of therapy. Beginning with Cycle 5, the dose of dexamethasone was reduced to 40 mg orally once daily on Days 1 to 4 for the remaining cycles.

Eligibility criteria: Inclusion Criteria:

* Prior or current diagnosis Durie-Salmon stage II or III multiple myeloma.
* No more than 3 previous anti-myeloma regimens
* No high-dose dexamethasone (total monthly dose of dexamethasone greater than 200 mg) within 6 months of study randomization.
* Measurable levels of myeloma paraprotein in serum or urine (24-hour collection sample).

Exclusion Criteria:

* Prior development of disease progression during high-dose dexamethasone containing therapy.
* Laboratory abnormalities: Absolute neutrophil count less than 1,000 cells/mm cubed
* Laboratory abnormalities: Platelet count less than 75,000/mm cubed
* Laboratory abnormalities: Serum creatinine greater than 2.5 mg/dL
* Laboratory abnormalities: Serum glutamic oxaloacetic transaminase (SGOT, aspartate transaminase \[AST\]) or serum glutamic pyruvic transaminase (SGPT, alanine transaminase \[ALT\])greater than 3.0 x upper limit of normal
* Laboratory abnormalities: Serum total bilirubin greater than 2.0 mg/dL
* Prior history of malignancies other than multiple myeloma unless the subject has been free of the disease for greater than or equal to 5 years.
* Known hypersensitivity to thalidomide or dexamethasone.
* Development of a desquamating rash while taking thalidomide.

Primary outcomes:
measure: Time to Tumor Progression (TTP)
timeFrame: 60 weeks (median Time To Progression of CC-5013/Dex treatment group)
Secondary outcomes:
measure: Overall Survival
timeFrame: 170 weeks (median overall survival of CC-5013/Dex treatment group)
measure: Myeloma Response
timeFrame: Up to Unblinding (07 Jun 2005)
measure: Time to First Worsening of Eastern Cooperative Oncology Group (ECOG) Performance Status Scale (Best Score=0, Fully Active, Able to Carry on All Pre-disease Performance Without Restriction; Worst Score=5, Dead.)
timeFrame: 30 weeks (mean time to first worsening of ECOG performance status for CC-5013/Dex treatment group)
Other outcomes:
Locations:
city: Hoover
country: United States
facility: Clinical Research Consultants, Inc.
state: Alabama
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA School of Medicine
state: California
city: San Francisco
country: United States
facility: UCSF California
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center, Division of Hematology
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic- Jacksonville
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Sarasota
country: United States
facility: Oncology Hematology Consultants
state: Florida
city: Tampa
country: United States
facility: H Lee Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Augusta
country: United States
facility: Medical College of Georgia
state: Georgia
city: Chicago
country: United States
facility: Northwestern University Med Ctr
state: Illinois
city: Chicago
country: United States
facility: Rush Cancer Institute Section of Hematology
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Cancer Research Institute
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospital Clinic
state: Iowa
city: New Orleans
country: United States
facility: Ocshner Clinical Foundation
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Medicine Department of Oncology
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University Of Michigan Comprehensive Cancer Center
state: Michigan
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine- Sherman Cancer Center
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: St. Vincent's Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: The Bronx
country: United States
facility: MBCCOP Our Lady of Mercy Cancer Center New York Medical College
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University School of Medicine
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Myeloma Program
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Portland
country: United States
facility: Kaiser Permanente Northwest Region Center for Health Research
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Charleston
country: United States
facility: Charleston Hematology/Oncology P.A.
state: South Carolina
city: Charleston
country: United States
facility: Medical University of SC
state: South Carolina
city: West Columbia
country: United States
facility: South Carolina Oncology Group
state: South Carolina
city: Nashville
country: United States
facility: Sarah Cannon Cancer Center
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Milwaukee
country: United States
facility: Froedtert Hospital/BMT Medical College of Wisconsin
state: Wisconsin
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Halifax
country: Canada
facility: Dalhousie University
state: Nova Scotia
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Greenfield Park
country: Canada
facility: Hospital Charles LeMoyne
state: Quebec
city: Montreal
country: Canada
facility: McGill University
state: Quebec
Study officials:
affiliation: Celgene Corporation
name: Robert Knight, MD
role: STUDY_DIRECTOR
References:
citation: Weber DM, Chen C, Niesvizky R, Wang M, Belch A, Stadtmauer EA, Siegel D, Borrello I, Rajkumar SV, Chanan-Khan AA, Lonial S, Yu Z, Patin J, Olesnyckyj M, Zeldis JB, Knight RD; Multiple Myeloma (009) Study Investigators. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med. 2007 Nov 22;357(21):2133-42. doi: 10.1056/NEJMoa070596.
citation: San-Miguel JF, Dimopoulos MA, Stadtmauer EA, Rajkumar SV, Siegel D, Bravo ML, Olesnyckyj M, Knight RD, Zeldis JB, Harousseau JL, Weber DM. Effects of lenalidomide and dexamethasone treatment duration on survival in patients with relapsed or refractory multiple myeloma treated with lenalidomide and dexamethasone. Clin Lymphoma Myeloma Leuk. 2011 Feb;11(1):38-43. doi: 10.3816/CLML.2010.n.120.
citation: Zangari M, Tricot G, Polavaram L, Zhan F, Finlayson A, Knight R, Fu T, Weber D, Dimopoulos MA, Niesvizky R, Fink L. Survival effect of venous thromboembolism in patients with multiple myeloma treated with lenalidomide and high-dose dexamethasone. J Clin Oncol. 2010 Jan 1;28(1):132-5. doi: 10.1200/JCO.2009.23.0169. Epub 2009 Nov 9.
citation: Wang M, Dimopoulos MA, Chen C, Cibeira MT, Attal M, Spencer A, Rajkumar SV, Yu Z, Olesnyckyj M, Zeldis JB, Knight RD, Weber DM. Lenalidomide plus dexamethasone is more effective than dexamethasone alone in patients with relapsed or refractory multiple myeloma regardless of prior thalidomide exposure. Blood. 2008 Dec 1;112(12):4445-51. doi: 10.1182/blood-2008-02-141614. Epub 2008 Sep 17.