NCT00424047 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2017-10-19

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."

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Kaplan-Meier Estimate of Time to Tumor Progression (TTP)

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outcome · POSTED

Kaplan-Meier Estimate of Overall Survival (OS)

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outcome · POSTED

Kaplan-Meier Estimate of Overall Survival (OS) (Later Cut-off Date of 02 March 2008)

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outcome · POSTED

Summary of Myeloma Response Rates Based on Best Response Assessment

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outcome · POSTED

Myeloma Response Rates Based on the Reviewers Best Response Assessment (Later Cut-off Date of 02 March 2008)

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outcome · POSTED

Number of Participants With Adverse Events (AE)

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outcome · POSTED

Time to First Symptomatic Skeletal-related Event (SRE) (Clinical Need for Radiation or Surgery to Bone)

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outcome · POSTED

Kaplan-Meier Estimate of Duration of Response

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outcome · POSTED

Kaplan-Meier Estimate of Time to Tumor Progression (TTP) (Later Cut-off Date of 02 Mar 2008)

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outcome · POSTED

Time to First Worsening on the Eastern Cooperative Oncology Group (ECOG) Performance Scale

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outcome · POSTED

Time to First Worsening on the Eastern Cooperative Oncology Group (ECOG) Performance Scale (Later Cut-off Date of 02 March 2008)

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outcome · POSTED

Kaplan-Meier Estimate of Duration of Response (Cut-off at a Later Date of 03 March 2008)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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.
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
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 Names
Drug: CC-5013 plus dexamethasone
label
CC-5013 plus dexamethasone
type
EXPERIMENTAL
description
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 Names
Drug: Dexamethasone plus Placebo
label
Dexamethasone plus placebo
type
EXPERIMENTAL

interventions

arm Group Labels
CC-5013 plus dexamethasone
description
25 mg daily for 21 days every 28 days.
name
CC-5013 plus dexamethasone
other Names
Revlimid
lenalidomide
type
DRUG
arm Group Labels
Dexamethasone plus placebo
description
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.
name
Dexamethasone plus Placebo
other Names
Dexamethasone
Placebo
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: QUADRUPLE
who Masked: PARTICIPANT
CARE_PROVIDER
INVESTIGATOR
OUTCOMES_ASSESSOR

primary Purpose

TREATMENT

Enrollment

count: 351
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
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
description
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.
measure
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

secondary Outcomes

description
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.
measure
Kaplan-Meier Estimate of Overall Survival (OS)
time Frame
Randomization to data cut off of 03 August 2005; up to 24 months
description
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.
measure
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
description
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.
measure
Summary of Myeloma Response Rates Based on Best Response Assessment
time Frame
Randomization to 03 August 2005; up to 24 months
description
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.
measure
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
description
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.
measure
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
description
Time from randomization to the date of the first occurrence of a symptomatic SRE (clinical need for radiotherapy or surgery to bone).
measure
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
description
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.
measure
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
description
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.
measure
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

Full study description

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."

Source references

references

citation
Dimopoulos M, Spencer A, Attal M, Prince HM, Harousseau JL, Dmoszynska A, San Miguel J, Hellmann A, Facon T, Foa R, Corso A, Masliak Z, Olesnyckyj M, Yu Z, Patin J, Zeldis JB, Knight RD; Multiple Myeloma (010) Study Investigators. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med. 2007 Nov 22;357(21):2123-32. doi: 10.1056/NEJMoa070594.
pmid
18032762
type
RESULT
citation
San-Miguel JF, Dimopoulos MA, Stadtmauer EA, Rajkumar SV, Siegel D, Bravo ML, Olesnyckyj M, Knight RD, Zeldis JB, Harousseau JL, Weber DM. Effects of lenalidomide and dexamethasone treatment duration on survival in patients with relapsed or refractory multiple myeloma treated with lenalidomide and dexamethasone. Clin Lymphoma Myeloma Leuk. 2011 Feb;11(1):38-43. doi: 10.3816/CLML.2010.n.120.
pmid
21273172
type
DERIVED
citation
Zangari M, Tricot G, Polavaram L, Zhan F, Finlayson A, Knight R, Fu T, Weber D, Dimopoulos MA, Niesvizky R, Fink L. Survival effect of venous thromboembolism in patients with multiple myeloma treated with lenalidomide and high-dose dexamethasone. J Clin Oncol. 2010 Jan 1;28(1):132-5. doi: 10.1200/JCO.2009.23.0169. Epub 2009 Nov 9.
pmid
19901114
type
DERIVED
citation
Wang M, Dimopoulos MA, Chen C, Cibeira MT, Attal M, Spencer A, Rajkumar SV, Yu Z, Olesnyckyj M, Zeldis JB, Knight RD, Weber DM. Lenalidomide plus dexamethasone is more effective than dexamethasone alone in patients with relapsed or refractory multiple myeloma regardless of prior thalidomide exposure. Blood. 2008 Dec 1;112(12):4445-51. doi: 10.1182/blood-2008-02-141614. Epub 2008 Sep 17.
pmid
18799726
type
DERIVED