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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01029262




Registration number
NCT01029262
Ethics application status
Date submitted
8/12/2009
Date registered
9/12/2009
Date last updated
25/06/2019

Titles & IDs
Public title
A Study of Lenalidomide Versus Placebo in Subjects With Transfusion Dependent Anemia in Lower Risk Myelodysplastic Syndrome (MDS) Without Del 5q
Scientific title
A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study To Compare The Efficacy And Safety of Lenalidomide (Revlimid®) Versus Placebo In Subjects With Transufsion-Dependent Anemia Due to IPSS Low Or Imtermidate-1 Risk Myelodysplastic Syndromes Without Deletion 5Q(31) And Unresponsive Or Refractory To Erthropoiesis-Stimulating Agents
Secondary ID [1] 0 0
CC-5013-MDS-005
Universal Trial Number (UTN)
Trial acronym
MDS-005
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anemia 0 0
Condition category
Condition code
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Anaemia
Blood 0 0 0 0
Other blood disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Lenalidomide
Other interventions - Placebo

Experimental: Arm #1 - Lenalidomide plus placebo - Lenalidomide 10 mg by mouth (PO) daily plus 2 placebo capsules for participants with a creatinine clearance = 60 mL/min for at least 168 days until disease progression, intolerable side effects or withdrawal of consent. Lenalidomide 5 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance = 40 and \< 60 mL/min.

Placebo comparator: Arm #2 - placebo - Three placebo capsules once daily for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent.


Treatment: Drugs: Lenalidomide
One 10 mg Lenalidomide capsule + 2 placebo capsules or (3 placebo capsules) once daily for subjects with a creatinine clearance = 60 mL/min. Alternatively-one 5 mg Lenalidomide capsule + 2 placebo capsules (or 3 placebo capsules) once daily for subjects with a creatinine clearance between 40 and 60 mL/min. Subjects may take study drug for at least 168 days unless there are intolerable side effects or disease progresses. Subjects may continue study drug beyond 168 days if they have an erythroid response (increase in their hemoglobin levels and fewer transfusions administered than before starting study drug)

Other interventions: Placebo
3 placebo capsules once daily. Subjects may take study drug for at least 168 days unless there are intolerable side effects or disease progresses. Subjects may continue study drug beyond 168 days if they have an erythroid response (increase in their hemoglobin levels and fewer transfusions administered than before starting study drug)
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence for = 56 Days as Determined by an Independent Review Committee (IRC)
Timepoint [1] 0 0
From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.
Primary outcome [2] 0 0
Percentage of Participants With a Erythroid Gene Signature Who Achieved RBC Transfusion Independence for = 56 Days as Determined by an Independent Review Committee (IRC)
Timepoint [2] 0 0
From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.
Secondary outcome [1] 0 0
Percentage of Participants Who Achieved RBC Transfusion Independence With a Duration of = 24 Weeks (168 Days) as Determined by the Sponsor
Timepoint [1] 0 0
From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.
Secondary outcome [2] 0 0
Kaplan Meier Estimates of Duration of 56-day RBC Transfusion Independence Response as Determined by the Sponsor
Timepoint [2] 0 0
Response was assessed up to the end of treatment; up to the data cut-off date of 17 Mar 2014.
Secondary outcome [3] 0 0
Percentage of Participants Who Achieved an Erythroid Response Based on the Modified International Working Group (IWG) 2006 Criteria
Timepoint [3] 0 0
From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.
Secondary outcome [4] 0 0
Time to 56-Day RBC-Transfusion-Independent (TI) Response as Determined by the Sponsor
Timepoint [4] 0 0
From first dose of study drug until 28 days after the last dose of study drug, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.
Secondary outcome [5] 0 0
Kaplan Meier Estimates for Progression to Acute Myeloid Leukemia (AML)
Timepoint [5] 0 0
From randomization to final data cut-off date of 03 Jul 2018; median follow up time for progression to AML was 2.3 years (range = 0 to 5.0 years) in the placebo arm and 2.6 years (range = 0 to 6.4 years) in the lenalidomide arm.
Secondary outcome [6] 0 0
Kaplan Meier Estimate for Overall Survival (OS)
Timepoint [6] 0 0
From randomization to final data cut-off date of 03 July 2018; maximum survival follow up was 6.4 years
Secondary outcome [7] 0 0
Number of Participants With Treatment Emergent Adverse Events (TEAE)
Timepoint [7] 0 0
From the first dose of study drug through 28 days after discontinuation from the study treatment; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide arm and 529 days in the placebo arm.
Secondary outcome [8] 0 0
Compliance Rates Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) From Baseline to Week 48
Timepoint [8] 0 0
Baseline, Week 12, (±3 days), Week 24, (±3 days), Week 36, (±3 days), and Week 48 (±3 days); up to data cut-off of 17 Mar 2014
Secondary outcome [9] 0 0
Mean Change From Baseline in the EORTC QLQ-C30 Fatigue Domain at Week 12 and 24
Timepoint [9] 0 0
Baseline and Week 12, ±3 days and Week 24, ±3 days
Secondary outcome [10] 0 0
Mean Change From Baseline in the EORTC QLQ-C30 Dyspnea Domain at Week 12 and 24
Timepoint [10] 0 0
Baseline and Week 12, ±3 days and Week 24, ±3 days
Secondary outcome [11] 0 0
Mean Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain at Week 12 and 24
Timepoint [11] 0 0
Baseline and Week 12, ±3 days and Week 24, ±3 days
Secondary outcome [12] 0 0
Mean Change From Baseline in the EORTC QLQ-C30 Global Health Status/Quality of Life (QOL) Domain at Week 12 and 24
Timepoint [12] 0 0
Baseline and Week 12, ±3 days and Week 24, ±3 days
Secondary outcome [13] 0 0
Mean Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain at Week 12 and 24
Timepoint [13] 0 0
Baseline and Week 12, ±3 days and Week 24, ±3 days
Secondary outcome [14] 0 0
Mean Change From Baseline in Fatigue Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24
Timepoint [14] 0 0
Baseline, Week 12, ±3 days and Week 24, ±3 days
Secondary outcome [15] 0 0
Mean Change From Baseline in the Dyspnea Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24
Timepoint [15] 0 0
Baseline, Week 12, ±3 days and Week 24, ±3 days
Secondary outcome [16] 0 0
Mean Change From Baseline in the Physical Functioning Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24
Timepoint [16] 0 0
Baseline, Week 12, ±3 days and Week 24, ±3 days
Secondary outcome [17] 0 0
Mean Change From Baseline in the Global Health Status/QoL Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24
Timepoint [17] 0 0
Baseline, Week 12, ±3 days and Week 24, ±3 days
Secondary outcome [18] 0 0
Mean Change From Baseline in the Emotional Functioning Domain Associated With the EORTC QLQ-C30 Scale at Weeks 12 and 24
Timepoint [18] 0 0
Baseline, Week 12, ±3 days and Week 24, ±3 days
Secondary outcome [19] 0 0
Percentage of Participants With a Clinically Meaningful Improvement in QOL (EORTC QLQ-C-30 Scale) From Baseline in Fatigue Domain at Weeks 12 and 24
Timepoint [19] 0 0
Baseline, Week 12, ±3 days and Week 24, ±3 days
Secondary outcome [20] 0 0
Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline in the Dyspnea Domain at Weeks 12 and 24
Timepoint [20] 0 0
Baseline, Week 12, ±3 days and Week 24, ±3 days
Secondary outcome [21] 0 0
Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline Within the Physical Functioning Domain at Weeks 12 and 24
Timepoint [21] 0 0
Baseline, Week 12, ±3 days and Week 24, ±3 days
Secondary outcome [22] 0 0
Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline in the Global Health Status/QOL Domain at Weeks 12 and 24
Timepoint [22] 0 0
Baseline, Week 12, ±3 days and Week 24, ±3 days
Secondary outcome [23] 0 0
Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline in the Emotional Functioning Domain at Weeks 12 and 24
Timepoint [23] 0 0
Baseline, Week 12, ±3 days and Week 24, ±3 days
Secondary outcome [24] 0 0
Healthcare Resource Utilization (HRU): Rate of Inpatient Hospitalizations Related to Adverse Events Per Person Year
Timepoint [24] 0 0
From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.
Secondary outcome [25] 0 0
Healthcare Resource Utilization (HRU): Duration of Hospitalizations Due to Adverse Events
Timepoint [25] 0 0
From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.
Secondary outcome [26] 0 0
Healthcare Resource Utilization (HRU): Number of Days of Hospitalization Due to Adverse Events Per Person-Years
Timepoint [26] 0 0
From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.

Eligibility
Key inclusion criteria
* 18 years or older
* Diagnosis of low or intermediate-1 risk Myelodysplastic (MDS) with any chromosome karyotype except del 5q[31]
* Anemia that requires red blood cell transfusions
* Resistant to erythropoiesis stimulating agents (ESAs) or blood erythropoietin level > 500 mU/mL
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) = 2
* Must agree to follow pregnancy precautions as required by the protocol.
* Must agree to receive counseling related to teratogenic and other risks of lenalidomide
* Must agree not to donate blood or semen
* Must be willing to consent to two or more bone marrow aspirate procedures to be completed during study
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Subjects previously receiving immunomodulating or immunosuppressive agents, or epigenetic or deoxyribonucleic acid (DNA) modulation agents
* Allergic reaction to thalidomide
* Renal insufficiency creatinine clearance (CrC1)<40 mL/min by Cockcroft-Gault method)
* Prior history of cancer, other than MDS, unless the subject has been free of the disease for = 5 years. (Basal cell carcinoma of the skin, carcinoma in situ of the cervix, or stage Tumor (T) 1a or T1b prostate cancer is allowed)
* Absolute neutrophil count (ANC) < 500/uL
* Platelets < 50,000/uL
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3X upper limit of normal
* Uncontrolled hyperthyroidism or hypothyroidism
* Significant neuropathy
* Prior stem cell transplantation
* Anemia due to reasons other than MDS
* History of deep venous thrombosis (DVT) or pulmonary embolus (PE) within past 3 years
* Significant active cardiac disease within the past 6 months
* Known Human Immunodeficiency Virus (HIV) infection; known Hepatitis C infection or active Hepatitis B infection

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/01/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
9/05/2018
Sample size
Target
Accrual to date
Final
239
Recruitment in Australia
Recruitment state(s)
NSW,SA
Recruitment hospital [1] 0 0
Wollongong Hospital - Wollongong
Recruitment hospital [2] 0 0
Royal Adelaide Hospital Institute of Medical and Veterinary Science - Adelaide
Recruitment hospital [3] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 0 0
2500 - Wollongong
Recruitment postcode(s) [2] 0 0
5000 SA - Adelaide
Recruitment postcode(s) [3] 0 0
4102 - Woolloongabba
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
New Hampshire
Country [4] 0 0
United States of America
State/province [4] 0 0
New Jersey
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas
Country [7] 0 0
United States of America
State/province [7] 0 0
Wisconsin
Country [8] 0 0
Austria
State/province [8] 0 0
Innsbruck
Country [9] 0 0
Austria
State/province [9] 0 0
Linz
Country [10] 0 0
Austria
State/province [10] 0 0
Salzburg
Country [11] 0 0
Austria
State/province [11] 0 0
Weis
Country [12] 0 0
Austria
State/province [12] 0 0
Wien
Country [13] 0 0
Belgium
State/province [13] 0 0
Brugge
Country [14] 0 0
Belgium
State/province [14] 0 0
Brussels
Country [15] 0 0
Belgium
State/province [15] 0 0
Charleroi
Country [16] 0 0
Belgium
State/province [16] 0 0
Edegem
Country [17] 0 0
Belgium
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Liege
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Belgium
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Mons
Country [19] 0 0
Belgium
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Namur
Country [20] 0 0
Canada
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Alberta
Country [21] 0 0
Canada
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Manitoba
Country [22] 0 0
Canada
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Ontario
Country [23] 0 0
Canada
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Quebec
Country [24] 0 0
Czechia
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Brno
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Czechia
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Olomouc
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Czechia
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Prague
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Czechia
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Praha
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France
State/province [28] 0 0
Angers
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France
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Bobigny Cedex
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France
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La Tronche
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France
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Lille
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France
State/province [32] 0 0
Marseille cedex
Country [33] 0 0
France
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Paris Cedex
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Germany
State/province [34] 0 0
Dresden
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Germany
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Duesseldorf
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Germany
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Duisberg
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Germany
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Düesseldorf
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Germany
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Hannover
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Germany
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Heidelberg
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Germany
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Köln
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Germany
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Mannheim
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Germany
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München
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Israel
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Petach-Tikva
Country [44] 0 0
Israel
State/province [44] 0 0
Tel Hashomer
Country [45] 0 0
Israel
State/province [45] 0 0
Tel-Aviv
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Italy
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Alessandria
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Italy
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Bologna
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Italy
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Cagliari
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Italy
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Firenze
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Italy
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Naples
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Italy
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Orbassano
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Italy
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Rionero in Vulture
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Italy
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Roma
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Italy
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Udine
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Japan
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Hiroshima
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Japan
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Isehara City, Kanagawa
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Japan
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Kamogawa
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Japan
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Kanazawa
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Japan
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Nagasaki
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Japan
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Nagoya
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Japan
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Osaka
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Japan
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Sendai
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Japan
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Shibuya
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Japan
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Shimotsuke
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Japan
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Shinagawa
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Poland
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Gdansk
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Poland
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Lodz
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Poland
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Warsaw
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Portugal
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Coimbra
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Portugal
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Lisboa
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Portugal
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Porto
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Malaga
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Spain
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Palma de Mallorca
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Spain
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Salamanca
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Spain
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Sevilla
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Spain
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Valencia
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Turkey
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Ankara
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Turkey
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Antalya
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Turkey
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Istanbul
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Turkey
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Izimir
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United Kingdom
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Bournemouth
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United Kingdom
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Cardiff
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United Kingdom
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Leeds
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United Kingdom
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London
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United Kingdom
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Manchester
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United Kingdom
State/province [88] 0 0
Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Celgene
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Albert Hoenekopp, MD
Address 0 0
Celgene Corporation
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

TypeCitations or Other Details
Journal Santini V, Almeida A, Giagounidis A, Gropper S, Jo... [More Details]

Results are available at https://clinicaltrials.gov/study/NCT01029262