A Study of Lenalidomide Plus Dexamethasone Versus Dexamethasone Alone in Previously Treated Patients With Multiple Myeloma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT00424047
First received: January 17, 2007
Last updated: March 3, 2015
Last verified: March 2015
  Purpose

The study compared the efficacy of oral lenalidomide in combination with oral pulse high-dose dexamethasone to that of placebo and oral high-dose pulse dexamethasone as treatment for participants with relapsed or refractory multiple myeloma.


Condition Intervention Phase
Multiple Myeloma
Drug: Lenalidomide
Drug: Dexamethasone
Drug: Placebo
Phase 3

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 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.

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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:
  • Kaplan-Meier Estimate of Overall Survival (OS) [ Time Frame: Randomization to data cut off of 03 August 2005; up to 24 months ] [ Designated as safety issue: No ]
    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) [ Time Frame: Randomization to data cut off of 02 March 2008; up to 51 months ] [ Designated as safety issue: No ]
    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.

  • Summary of Myeloma Response Rates Based on Best Response Assessment [ Time Frame: Randomization to 03 August 2005; up to 24 months ] [ Designated as safety issue: No ]
    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.

  • Myeloma Response Rates Based on the Reviewers Best Response Assessment (Later Cut-off Date of 02 March 2008) [ Time Frame: Randomization to data cut-off of 02 Mar 2008; up to 51 months ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Adverse Events (AE) [ Time Frame: 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 ] [ Designated as safety issue: Yes ]

    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) [ Time Frame: Up to unblinding data cut off of 03 August 2005; up to 24 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Randomization to cut off date of 03 August 2005; up to 24 months ] [ Designated as safety issue: No ]
    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.

  • Time to First Worsening on the Eastern Cooperative Oncology Group (ECOG) Performance Scale (Later Cut-off Date of 02 March 2008) [ Time Frame: Randomization to cut off date of 02 March 2008; up to 51 months ] [ Designated as safety issue: No ]
    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.


Enrollment: 351
Study Start Date: September 2003
Study Completion Date: November 2013
Primary Completion Date: August 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lenalidomide plus dexamethasone
Lenalidomide was administered at a dose of 25 mg by mouth daily for 21 days every 28 days. The participant also received a matching placebo identical in appearance to the lenalidomide capsule daily on Day 22 to Day 28 of each 28 cycle. Oral pulse dexamethasone was 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 until disease progression. Beginning with Cycle 5, the oral dexamethasone dosing schedule was reduced to 40mg daily for Days 1-4 every 28 days.
Drug: Lenalidomide
25 mg Lenalidomide administered by mouth daily on Days 1-21 of each 28-day treatment cycle until disease progression.
Other Names:
  • Revlimid®
  • CC-5013
Drug: Dexamethasone
Oral pulse dexamethasone for oral administration
Other Name: Decadron
Drug: Placebo
Other Name: A matching placebo capsule
Experimental: Dexamethasone plus placebo
Oral pulse dexamethasone was administered at a dose of 40mg by mouth 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 was reduced to 40mg daily for Days 1-4 every 28 days until disease progression. In addition, oral placebo capsules were administered on Days 1 to 28 of each 28 cycle.
Drug: Dexamethasone
Oral pulse dexamethasone for oral administration
Other Name: Decadron
Drug: Placebo
Other Name: A matching placebo capsule

Detailed Description:

The study was initiated in 2003 and enrolled a total of 351 participants. The study was unblinded starting on 03 August 2005 after a preplanned interim analysis demonstrated a highly significant treatment benefit in favor of the lenalidomide/dexamethasone combination based on results for the primary endpoint, time to progression (TTP). In March 2008, the specified number of at least 194 death events needed for full statistical power of the overall survival (OS) analysis was reached.

At the time of the 02 March 2008 cutoff date, there were still 29 participants in active treatment in Europe (Austria, Belgium, France, Italy, Poland, Spain and Ukraine) and Israel. Only safety data were collected for these participants beyond the 02 March 2008 cutoff date. The last visit for the last patient occurred on 25 June 2013.

  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.
  • 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/mm^3
  • Laboratory abnormalities: Platelet count < 75,000/mm^3
  • Laboratory abnormalities: Serum creatinine > 2.5 mg/dL
  • Laboratory abnormalities: 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00424047

  Show 69 Study Locations
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: Robert Knight, MD Celgene Corporation
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT00424047     History of Changes
Other Study ID Numbers: CC-5013-MM-010
Study First Received: January 17, 2007
Results First Received: February 13, 2015
Last Updated: March 3, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Celgene Corporation:
Multiple Myeloma
Celgene
Revlimid
CC-5013

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
BB 1101
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Lenalidomide
Thalidomide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 05, 2015