A Study of CC-5013 Plus Dexamethasone Versus Dexamethasone Alone in Previously Treated Subjects With Multiple Myeloma
- Conditions
- Multiple Myeloma
- Interventions
- Registration Number
- NCT00424047
- Lead Sponsor
- Celgene
- Brief 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."
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 351
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dexamethasone plus placebo Dexamethasone plus Placebo Arm B: 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. CC-5013 plus dexamethasone CC-5013 plus dexamethasone Arm A: Oral CC-5013 is initiated on Day 1 of Cycle 1 at a dose of 25 mg daily for 21 days every 28 days. Therefore, the subject will take a placebo identical in appearance to the CC-5013 capsule for week 4 of every 28 days. 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 CC-5013 placebo capsules will be administered for 28 days of every cycle.
- Primary Outcome Measures
Name Time Method Kaplan-Meier Estimate of Time to Tumor Progression (TTP) From randomization up to cut-off date of 03 August 2005; up to 24 months 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.
Kaplan-Meier Estimate of Time to Tumor Progression (TTP) (Later Cut-off Date of 02 Mar 2008) From randomization up to cut-off date of 02 March 2008; up to 51 months 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.
- Secondary Outcome Measures
Name Time Method Summary of Myeloma Response Rates Based on Best Response Assessment Randomization to 03 August 2005; up to 24 months 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.
Kaplan-Meier Estimate of Overall Survival (OS) Randomization to data cut off of 03 August 2005; up to 24 months 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.
Kaplan-Meier Estimate of Overall Survival (OS) (Later Cut-off Date of 02 March 2008) Randomization to data cut off of 02 March 2008; up to 51 months 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.
Myeloma Response Rates Based on the Reviewers Best Response Assessment (Later Cut-off Date of 02 March 2008) Randomization to data cut-off of 02 Mar 2008; up to 51 months 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.
Time to First Worsening on the Eastern Cooperative Oncology Group (ECOG) Performance Scale Randomization to cut off date of 03 August 2005; up to 24 months 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.
Number of Participants With Adverse Events (AE) 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 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.Time to First Symptomatic Skeletal-related Event (SRE) (Clinical Need for Radiation or Surgery to Bone) Up to unblinding data cut off of 03 August 2005; up to 24 months Time from randomization to the date of the first occurrence of a symptomatic SRE (clinical need for radiotherapy or surgery to bone).
Time to First Worsening on the Eastern Cooperative Oncology Group (ECOG) Performance Scale (Later Cut-off Date of 02 March 2008) Randomization to cut off date of 02 March 2008; up to 51 months 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.
Trial Locations
- Locations (69)
University Hospital GalwayHaematology Department
🇮🇪Galway, Co. Galway, Ireland
Centre Hospitalier Universitaire Vaudois (CHUV)
🇨🇭Lausanne, Switzerland
Institute of Haematology and Blood Transfusion
🇵🇱Warsaw, Poland
Hospital Doce de Octubre
🇪🇸Madrid, Spain
The Alfred Hospital
🇦🇺Prahran, Victoria, Australia
MidWestern Regional Hospital
🇮🇪Limerick, Ireland
Universitatsklinik ChariteMedizinische Fakultaet der HumboldtUniversitaet zu Berlin
🇩🇪Berlin, Germany
Royal Prince Alfred Hospital
🇦🇺Camperdown, New South Wales, Australia
Chu de Bordeaux Groupe Hospitalier Sud
🇫🇷Pessac, France
Rambam Medical Center
🇮🇱Haifa, Israel
Hope Directorate Haematology Oncology Service St. James Hospital
🇮🇪Dublin 8, Ireland
"Alexandras" General Hospital of Athens
🇬🇷Athens, Greece
CHU Nancy - Hopital Brabois
🇫🇷Vandoeuvre, France
Centre Hospitalier Hotel-Dieu
🇫🇷Nantes, France
CHU Purpan
🇫🇷Toulouse cedex 9, France
The Chaim Sheba Medical Center
🇮🇱Tel Hashomer, Israel
Box Hill Hospital
🇦🇺Box Hill, Australia
Univerita La Sapien
🇮🇹Roma, Italy
The Royal Melbourne Hospital
🇦🇺Parkville, Australia
CHU Saint-Luc
🇧🇪Brussel, Belgium
Policlinico San Matteo
🇮🇹Pavia, Italy
Clinica Universitaria de Navarra
🇪🇸Pamplona, Spain
Centre Hospitalier Lyon Sud
🇫🇷Chemin Grand Revoyet, France
Universitaetsklinikum Dusseldorf Klinik fuer Haematologie
🇩🇪Dusseldorf, Germany
Hopital Claude Huriez
🇫🇷Lille, France
Frankston Hospital Oncology Research
🇦🇺Frankston, Australia
Wilhelminenspital
🇦🇹Vienna, Austria
Policlinico Universitario a Gesttione diretta di Udine
🇮🇹Udine, Italy
Mater Public Hospital
🇦🇺South Brisbane, Australia
Tel Aviv Sourasky Medical Center Department of Hematology
🇮🇱Tel Aviv, Israel
Klininkum der Johann-Wolfgang-Goethe-Universtat
🇩🇪Frankfurt am Main, Germany
Hospital Universitario de la Princessa
🇪🇸Madrid, Spain
Belfast City HospitalHaematology Department
🇮🇪Belfast, Ireland
Dnepropetrovsk City Clinical Hospital #4
🇺🇦Dnepropetrovsk, Ukraine
Hospital Clinic
🇪🇸Barcelona, Spain
Universitaetsklinkum Erlangen
🇩🇪Erlangen, Germany
Universitaetsklinikum Charite
🇩🇪Berlin, Germany
Policlinico Sant'Orsola-Malpighi
🇮🇹Bologna, Italy
Haematology Dept, 4th Floor Thomas Guy House
🇬🇧London, United Kingdom
University School of Medicine
🇵🇱Lublin, Poland
Institute of Hematology and Transfusiology of the UAMS Department of blood diseases
🇺🇦Kiev, Ukraine
Azienda Sanitaria Ospedaliera Molinette S. Giovanni Battista
🇮🇹Torio, Italy
Bristol Haematology and Oncology Centre
🇬🇧Bristol, United Kingdom
Universitätsspital Zürich
🇨🇭Zürich, Switzerland
Kiev Bone Marrow Transplantation Center Bone Marrow Department
🇺🇦Kiev, Ukraine
Kantonsspital St. Gallen
🇨🇭St. Gallen, Switzerland
Cherkassy Regional Oncology Center
🇺🇦Cherkassy, Ukraine
Zhitomir Regional Clinical Hospital
🇺🇦Zhitomir, Ukraine
Hospital Universtario Marques de Valdecilla
🇪🇸Santander, Spain
Hospital Universitario de Salamanca
🇪🇸Salamanca, Spain
Institute of Blood Pathology and Transfusion Medicine of the UAMS Hematology Department
🇺🇦Lvov, Ukraine
UZ Gasthuisberg
🇧🇪Leuven, Belgium
Klinikum der Univeristact Muenchen
🇩🇪Munchen, Germany
Peter MacCallum Cancer Centre Divsion of Haematology/Medical Oncology
🇦🇺East Melbourne, Victoria, Australia
Border Medical Oncology
🇦🇺Wodonga, Victoria, Australia
Royal Brisbane Hospital
🇦🇺Herston, Australia
University Hospital of Salzburg St Johanns Spital
🇦🇹Salzburg, Austria
Hopital Saint-Loius
🇫🇷Paris, France
Universitaetsklinikum Heidelberg Medizinische Klinik und Poliklinik V
🇩🇪Heidelberg, Germany
Azienda Ospedaliera San Martino
🇮🇹Genova, Italy
Universitatsklinik Muenster Medizinische Klinik A
🇩🇪Muenster, Germany
Universitaetsklinikum Tuebingen
🇩🇪Tubingen, Germany
Hadassah University Hospital
🇮🇱Jerusalem, Israel
Ospedale Niguarda Ca Granda
🇮🇹Milano, Italy
Institute of Internal Diseases University of Medicine
🇵🇱Gdansk, Poland
Sahlgrenska University Hospital Department of Hematology and Coagulation
🇸🇪Goteborg, Sweden
Institute of Blood Pathology and Transfusion Medicine of the UAMS
🇺🇦Lviv, Ukraine
University College Hospital Trust
🇬🇧London, Bloomsbury, United Kingdom
Odess Regional Clinical Hospital
🇺🇦Odessa, Ukraine