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

Phase 3

Completed

Conditions: Multiple Myeloma

Interventions: Drug: Dexamethasone plus Placebo
Drug: CC-5013 plus dexamethasone

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

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.

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): Royal Prince Alfred Hospital
🇦🇺
Camperdown, New South Wales, Australia
Peter MacCallum Cancer Centre Divsion of Haematology/Medical Oncology
🇦🇺
East Melbourne, Victoria, Australia
The Alfred Hospital
🇦🇺
Prahran, Victoria, Australia
Border Medical Oncology
🇦🇺
Wodonga, Victoria, Australia
Box Hill Hospital
🇦🇺
Box Hill, Australia
Frankston Hospital Oncology Research
🇦🇺
Frankston, Australia
Royal Brisbane Hospital
🇦🇺
Herston, Australia
The Royal Melbourne Hospital
🇦🇺
Parkville, Australia
Mater Public Hospital
🇦🇺
South Brisbane, Australia
University Hospital of Salzburg St Johanns Spital
🇦🇹
Salzburg, Austria
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Royal Prince Alfred Hospital
🇦🇺Camperdown, New South Wales, Australia