A Study of CC-5013 Plus Dexamethasone Versus Dexamethasone Alone in Previously Treated Subjects With Multiple Myeloma

Multiple Myeloma Clinical Trial

Official title:

The Official Title is A Multi-center, Randomized, Parallel-group, Double-blind, Placebo Controlled Study of CC-5013 Plus Dexamethasone Versus Dexamethasone Alone in Previously Treated Subjects With Multiple Myeloma.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00424047
• Other study ID #: CC-5013-MM-010
• Status: Completed
• Phase: Phase 3
• First received: January 17, 2007
• Last updated: September 18, 2017
• Start date: January 1, 2003
• Est. completion date: November 12, 2013

Study information

• Verified date: September 2017
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To compare the efficacy of oral CC-5013 in combination with oral pulse high-dose dexamethasone to that of placebo and oral high-dose pulse dexamethasone as treatment for subjects with relapsed or refractory multiple myeloma."

Recruitment information / eligibility

• Status: Completed
• Enrollment: 351
• Est. completion date: November 12, 2013
• Est. primary completion date: November 1, 2005
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Prior or current diagnosis Durie-Salmon stage II or III multiple myeloma.

• Measurable levels of myeloma paraprotein in serum or urine (24-hour collection sample).

• Eastern Cooperative Oncology Group (ECOG) performance status score of 0,1, or 2

• Females of childbearing potential must have a negative serum or urine pregnancy test within 7 days of starting study drug

Exclusion Criteria:

• Prior development of disease progression during high-dose dexamethasone containing therapy

• Pregnant or lactating females

• The development of a desquamating rash while taking thalidomide

• Use of any standard/experimental anti-myeloma therapy within 28 days of randomization or use of any experimental non-drug therapy within 56 days of initiation of drug treatment

• Laboratory abnormalities: Absolute neutrophil count less than 1,000 cells/mm3

• Laboratory abnormalities: Platelet count < 75,000/mm3

• Laboratory abnormalities: Serum creatinine > 2.5 mg/dL

• Laboratory abnormalities: Serum Serum glutamic oxaloacetic transaminase (SGOT)/Aspartate aminotransferase (AST) or Serum glutamic pyruvic transaminase (SGPT)/Alanine aminotransferase (ALT) > 3.0 x upper limit of normal

• Laboratory abnormalities: Serum total bilirubin > 2.0 mg/dL

• Prior history of malignancies other than multiple myeloma unless the subject has been free of the disease for = 3 years.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• CC-5013 plus dexamethasone
25 mg daily for 21 days every 28 days.
• Dexamethasone plus Placebo
Oral pulse dexamethasone is administered at a dose of 40mg daily on Days 1-4, 9-12, and 17-20 of each 28 day cycle for Cycles 1 through 4. Beginning with Cycle 5, the oral dexamethasone dosing schedule will be reduced to 40mg daily for Days 1-4 every 28 days. In addition, oral placebo capsules will be administered for 28 days of every cycle.

Locations

Country	Name	City	State
Australia	Box Hill Hospital	Box Hill
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Peter MacCallum Cancer Centre Divsion of Haematology/Medical Oncology	East Melbourne	Victoria
Australia	Frankston Hospital Oncology Research	Frankston
Australia	Royal Brisbane Hospital	Herston
Australia	The Royal Melbourne Hospital	Parkville
Australia	The Alfred Hospital	Prahran	Victoria
Australia	Mater Public Hospital	South Brisbane
Australia	Border Medical Oncology	Wodonga	Victoria
Austria	University Hospital of Salzburg St Johanns Spital	Salzburg
Austria	Wilhelminenspital	Vienna
Belgium	CHU Saint-Luc	Brussel
Belgium	UZ Gasthuisberg	Leuven
France	Centre Hospitalier Lyon Sud	Chemin Grand Revoyet
France	Hopital Claude Huriez	Lille
France	Centre Hospitalier Hotel-Dieu	Nantes
France	Hopital Saint-Loius	Paris
France	Chu de Bordeaux Groupe Hospitalier Sud	Pessac
France	CHU Purpan	Toulouse cedex 9
France	CHU Nancy - Hopital Brabois	Vandoeuvre
Germany	Universitaetsklinikum Charite	Berlin
Germany	Universitatsklinik ChariteMedizinische Fakultaet der HumboldtUniversitaet zu Berlin	Berlin
Germany	Universitaetsklinikum Dusseldorf Klinik fuer Haematologie	Dusseldorf
Germany	Universitaetsklinkum Erlangen	Erlangen
Germany	Klininkum der Johann-Wolfgang-Goethe-Universtat	Frankfurt am Main
Germany	Universitaetsklinikum Heidelberg Medizinische Klinik und Poliklinik V	Heidelberg
Germany	Universitatsklinik Muenster Medizinische Klinik A	Muenster
Germany	Klinikum der Univeristact Muenchen	Munchen
Germany	Universitaetsklinikum Tuebingen	Tubingen
Greece	"Alexandras" General Hospital of Athens	Athens
Ireland	Belfast City HospitalHaematology Department	Belfast
Ireland	Hope Directorate Haematology Oncology Service St. James Hospital	Dublin 8
Ireland	University Hospital GalwayHaematology Department	Galway	Co. Galway
Ireland	MidWestern Regional Hospital	Limerick
Israel	Rambam Medical Center	Haifa
Israel	Hadassah University Hospital	Jerusalem
Israel	Tel Aviv Sourasky Medical Center Department of Hematology	Tel Aviv
Israel	The Chaim Sheba Medical Center	Tel Hashomer
Italy	Policlinico Sant'Orsola-Malpighi	Bologna
Italy	Azienda Ospedaliera San Martino	Genova
Italy	Ospedale Niguarda Ca Granda	Milano
Italy	Policlinico San Matteo	Pavia
Italy	Univerita La Sapien	Roma
Italy	Azienda Sanitaria Ospedaliera Molinette S. Giovanni Battista	Torio
Italy	Policlinico Universitario a Gesttione diretta di Udine	Udine
Poland	Institute of Internal Diseases University of Medicine	Gdansk
Poland	University School of Medicine	Lublin
Poland	Institute of Haematology and Blood Transfusion	Warsaw
Spain	Hospital Clinic	Barcelona
Spain	Hospital Doce de Octubre	Madrid
Spain	Hospital Universitario de la Princessa	Madrid
Spain	Clinica Universitaria de Navarra	Pamplona
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital Universtario Marques de Valdecilla	Santander
Sweden	Sahlgrenska University Hospital Department of Hematology and Coagulation	Goteborg
Switzerland	Centre Hospitalier Universitaire Vaudois (CHUV)	Lausanne
Switzerland	Kantonsspital St. Gallen	St. Gallen
Switzerland	Universitätsspital Zürich	Zürich
Ukraine	Cherkassy Regional Oncology Center	Cherkassy
Ukraine	Dnepropetrovsk City Clinical Hospital #4	Dnepropetrovsk
Ukraine	Institute of Hematology and Transfusiology of the UAMS Department of blood diseases	Kiev
Ukraine	Kiev Bone Marrow Transplantation Center Bone Marrow Department	Kiev
Ukraine	Institute of Blood Pathology and Transfusion Medicine of the UAMS	Lviv
Ukraine	Institute of Blood Pathology and Transfusion Medicine of the UAMS Hematology Department	Lvov
Ukraine	Odess Regional Clinical Hospital	Odessa
Ukraine	Zhitomir Regional Clinical Hospital	Zhitomir
United Kingdom	Bristol Haematology and Oncology Centre	Bristol
United Kingdom	Haematology Dept, 4th Floor Thomas Guy House	London
United Kingdom	University College Hospital Trust	London	Bloomsbury

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

Australia,  Austria,  Belgium,  France,  Germany,  Greece,  Ireland,  Israel,  Italy,  Poland,  Spain,  Sweden,  Switzerland,  Ukraine,  United Kingdom, 

References & Publications (1)

Dimopoulos M, Spencer A, Attal M, Prince HM, Harousseau JL, Dmoszynska A, San Miguel J, Hellmann A, Facon T, Foà R, Corso A, Masliak Z, Olesnyckyj M, Yu Z, Patin J, Zeldis JB, Knight RD; Multiple Myeloma (010) Study Investigators. Lenalidomide plus dexame — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Kaplan-Meier Estimate of Time to Tumor Progression (TTP)	Time to progression was calculated as the time from randomization to the first occurrence of disease progression, as determined by a detailed review of all the myeloma response assessment data using the Bladé criteria (Bladé, 1998). Disease progression was also based on bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia.	From randomization up to cut-off date of 03 August 2005; up to 24 months
Primary	Kaplan-Meier Estimate of Time to Tumor Progression (TTP) (Later Cut-off Date of 02 Mar 2008)	Time to progression was calculated as the time from randomization to the first occurrence of disease progression, as determined by a detailed review of all the myeloma response assessment data using the Bladé criteria (Bladé, 1998). Disease progression was also based on bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia.	From randomization up to cut-off date of 02 March 2008; up to 51 months
Secondary	Kaplan-Meier Estimate of Overall Survival (OS)	OS was calculated as the time from randomization to death from any cause. OS was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who were lost to follow-up before death was documented.	Randomization to data cut off of 03 August 2005; up to 24 months
Secondary	Kaplan-Meier Estimate of Overall Survival (OS) (Later Cut-off Date of 02 March 2008)	OS was calculated as the time from randomization to death from any cause. OS was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who were lost to follow-up before death was documented.	Randomization to data cut off of 02 March 2008; up to 51 months
Secondary	Summary of Myeloma Response Rates Based on Best Response Assessment	Complete Response (CR): Disappearance of monoclonal paraprotein and maintained for = 6 weeks . Remission Response (RR):75-99% reduction in the level of the serum monoclonal paraprotein compared to baseline; 90-99% reduction in 24-hr urinary light chain excretion. Partial Response (PR): 50-74% reduction in the level of monoclonal paraprotein compared to baseline; 50-89% reduction in 24-hr urinary light chain excretion. Stable Disease (SD): Criteria for PR or PD have not been met. Plateau Phase: If PR, stable monoclonal paraprotein values (within 25% above or below nadir)/stable soft tissue plasmacytomas maintained for at least 3 months. Progressive Disease (PD): Reappearance of serum or urinary monoclonal paraprotein on immunofixation or electrophoresis on two consecutive occasions at least one week apart. Increase of percentage of plasma cells in bone marrow aspirate or biopsy to = 5%. Development of at least one new lytic bone lesion or soft tissue plasmacytoma.	Randomization to 03 August 2005; up to 24 months
Secondary	Myeloma Response Rates Based on the Reviewers Best Response Assessment (Later Cut-off Date of 02 March 2008)	Complete Response (CR): Disappearance of monoclonal paraprotein and maintained for = 6 weeks . Remission Response (RR):75-99% reduction in the level of the serum monoclonal paraprotein compared to baseline; 90-99% reduction in 24-hr urinary light chain excretion. Partial Response (PR): 50-74% reduction in the level of monoclonal paraprotein compared to baseline; 50-89% reduction in 24-hr urinary light chain excretion. Stable Disease (SD): Criteria for PR or PD have not been met. Plateau Phase: If PR, stable monoclonal paraprotein values (within 25% above or below nadir)/stable soft tissue plasmacytomas maintained for at least 3 months. Progressive Disease (PD): Reappearance of serum or urinary monoclonal paraprotein on immunofixation or electrophoresis on two consecutive occasions at least one week apart. Increase of percentage of plasma cells in bone marrow aspirate or biopsy to = 5%. Development of at least one new lytic bone lesion or soft tissue plasmacytoma.	Randomization to data cut-off of 02 Mar 2008; up to 51 months
Secondary	Number of Participants With Adverse Events (AE)	An AE is any sign, symptom, illness, or diagnosis that appears or worsens during the course of the study. Treatment-emergent AEs (TEAEs) are any AE occurring or worsening on or after the first treatment of the study drug and within 30 days after the last cycle end date of study drug. A serious AE = any AE which results in death; is life-threatening; requires or prolongs existing inpatient hospitalization; results in persistent or significant disability is a congenital anomaly/birth defect; constitutes an important medical event.; The severity of AEs were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE, Version 2.0): Grade 1 = Mild (no limitation in activity or intervention required); Grade 2 = Moderate (some limitation in activity; no/minimal medical intervention required); Grade 3 = Severe (marked limitation in activity; medical intervention required, hospitalization possible); Grade 4 = Life-threatening; Grade 5 = Death.	From first dose of study drug through to 30 days after the last dose, until the data cut-off date of 25 June 2013; up to 90 months
Secondary	Time to First Symptomatic Skeletal-related Event (SRE) (Clinical Need for Radiation or Surgery to Bone)	Time from randomization to the date of the first occurrence of a symptomatic SRE (clinical need for radiotherapy or surgery to bone).	Up to unblinding data cut off of 03 August 2005; up to 24 months
Secondary	Time to First Worsening on the Eastern Cooperative Oncology Group (ECOG) Performance Scale	The time to first worsening of the ECOG performance status was calculated as the time from randomization to the date of the first worsening compared with the last ECOG evaluation obtained prior to randomization. Data were censored at the last date that the participant was known to be unchanged or improved from before randomization for the participants who had not had worsened at the time of the analysis and for the patients who were lost to follow-up before worsening in the ECOG performance status was documented.	Randomization to cut off date of 03 August 2005; up to 24 months
Secondary	Time to First Worsening on the Eastern Cooperative Oncology Group (ECOG) Performance Scale (Later Cut-off Date of 02 March 2008)	The time to first worsening of the ECOG performance status was calculated as the time from randomization to the date of the first worsening compared with the last ECOG evaluation obtained prior to randomization. Data were censored at the last date that the participant was known to be unchanged or improved from before randomization for the participants who had not had worsened at the time of the analysis and for the patients who were lost to follow-up before worsening in the ECOG performance status was documented.	Randomization to cut off date of 02 March 2008; up to 51 months

External Links

•   Link to CSR synopsis