CC-5013 Plus Dexamethasone Versus Dexamethasone Alone in Previously Treated Subjects With Multiple Myeloma - Full Text View

Sponsor:	Celgene Corporation
Information provided by:	Celgene Corporation
ClinicalTrials.gov Identifier:	NCT00056160

Purpose

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.

Condition	Intervention	Phase
Multiple Myeloma	Drug: CC-5013 Drug: Dexamethasone	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
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

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Cancer Multiple Myeloma

Drug Information available for: Dexamethasone Dexamethasone acetate Doxiproct plus Lenalidomide CC 5013 Dexamethasone Sodium Phosphate

U.S. FDA Resources

Further study details as provided by Celgene Corporation:

Primary Outcome Measures:

Time to Tumor Progression (TTP) [ Time Frame: 60 weeks (median Time To Progression of CC-5013/Dex treatment group) ] [ Designated as safety issue: No ]
Time to progression (TTP) was calculated as the time from randomization to the first documentation of progressive disease based on the myeloma response determination criteria developed by Bladé et. al., Br J Haematol 1998; 102:1115-1123.

Secondary Outcome Measures:

Overall Survival [ Time Frame: 170 weeks (median overall survival of CC-5013/Dex treatment group) ] [ Designated as safety issue: No ]
Overall survival was calculated as the time from randomization to death from any cause.
Myeloma Response [ Time Frame: Up to Unblinding (07 Jun 2005) ] [ Designated as safety issue: No ]
The overall confirmed response that was maintained for ≥6 weeks. Complete Response (CR):Disappearance of monoclonal paraprotein. Remission Response (RR):75-99% reduction in monoclonal paraprotein/90-99% reduction in 24-hr urinary light chain excretion. Partial Response (PR):50-74% reduction in monoclonal paraprotein/50-89% reduction in 24-hr urinary light chain excretion. Stable Disease (SD):Criteria for PR or PD not met. Plateau Phase:If PR, stable monoclonal paraprotein (within 25% above or below nadir)/stable soft tissue plasmacytomas. Progressive Disease (PD):Disease worsens.
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.) [ Time Frame: 30 weeks (mean time to first worsening of ECOG performance status for CC-5013/Dex treatment group) ] [ Designated as safety issue: No ]
The time to first worsening on the ECOG Performance Scale was calculated as the time from randomization to the date of the first worsening compared to the last ECOG evaluation obtained prior to randomization.

Enrollment:	353
Study Start Date:	January 2003
Study Completion Date:	October 2008
Primary Completion Date:	November 2005 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: CC-5013/Dex CC-5013 (lenalidomide) plus oral high-dose dexamethasone	Drug: CC-5013 Subjects in the CC-5013/Dex treatment group took 25 mg of lenalidomide 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. Other Names: CC-5013 lenalidomide Revlimid Drug: Dexamethasone Subjects in the CC-5013/Dex and Placebo/Dex 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. Other Names: dexamethasone Decadron
Experimental: Placebo/Dex Placebo, identical in appearance to CC-5013 (lenalidomide), plus oral high-dose dexamethasone	Drug: Dexamethasone Subjects in the CC-5013/Dex and Placebo/Dex 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. Other Names: dexamethasone Decadron

Arms

Assigned Interventions

Experimental: CC-5013/Dex

CC-5013 (lenalidomide) plus oral high-dose dexamethasone

Drug: CC-5013

Subjects in the CC-5013/Dex treatment group took 25 mg of lenalidomide 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.

Other Names:

CC-5013
lenalidomide
Revlimid

Drug: Dexamethasone

Subjects in the CC-5013/Dex and Placebo/Dex 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.

Other Names:

dexamethasone
Decadron

Experimental: Placebo/Dex

Placebo, identical in appearance to CC-5013 (lenalidomide), plus oral high-dose dexamethasone

Drug: Dexamethasone

Subjects in the CC-5013/Dex and Placebo/Dex 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.

Other Names:

dexamethasone
Decadron

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00056160

Show 49 Study Locations

Sponsors and Collaborators

Celgene Corporation

Investigators

Study Director:

Robert Knight, MD

Celgene Corporation

More Information

No publications provided by Celgene Corporation

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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 1;11(1):38-43.

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. Epub 2009 Nov 9.

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. Epub 2008 Sep 17.

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.

Responsible Party:	Robert Knight MD - Vice President, Oncology, Celgene Corporation
ClinicalTrials.gov Identifier:	NCT00056160 History of Changes
Other Study ID Numbers:	CC-5013-MM-009
Study First Received:	March 6, 2003
Results First Received:	December 24, 2009
Last Updated:	March 10, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by Celgene Corporation:

Multiple Myeloma
Refractory and Relapsed
Revlimid
CC5013

Additional relevant MeSH terms:

Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate

Dexamethasone
Dexamethasone 21-phosphate
Lenalidomide
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones

ClinicalTrials.gov processed this record on February 09, 2012