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.
Overview
- Phase
- Phase 3
- Intervention
- CC-5013 plus dexamethasone
- Conditions
- Multiple Myeloma
- Sponsor
- Celgene
- Enrollment
- 351
- Locations
- 69
- Primary Endpoint
- Kaplan-Meier Estimate of Time to Tumor Progression (TTP)
- Status
- Completed
- Last Updated
- 8 years ago
Overview
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."
Investigators
Eligibility Criteria
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.
Arms & Interventions
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.
Intervention: CC-5013 plus dexamethasone
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.
Intervention: Dexamethasone plus Placebo
Outcomes
Primary Outcomes
Kaplan-Meier Estimate of Time to Tumor Progression (TTP)
Time Frame: 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)
Time Frame: 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 Outcomes
- Summary of Myeloma Response Rates Based on Best Response Assessment(Randomization to 03 August 2005; up to 24 months)
- Kaplan-Meier Estimate of Overall Survival (OS)(Randomization to data cut off of 03 August 2005; up to 24 months)
- 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)
- 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)
- 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)
- 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)
- 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 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)