Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

A Study of Lenalidomide Versus Placebo in Subjects With Transfusion Dependent Anemia in Lower Risk Myelodysplastic Syndrome (MDS) Without Del 5q (MDS-005)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01029262
First received: December 8, 2009
Last updated: May 25, 2016
Last verified: May 2016
Results First Received: May 8, 2015  
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
Condition: Anemia
Interventions: Drug: Lenalidomide
Other: Placebo

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were randomized in a blinded manner receiving either oral lenalidomide or placebo daily. The study is on-going for an overall duration of 5 years. Participants continue to be followed for transfusion independence, safety events, survival, progression and subsequent therapies. The data is reported up to a cut-off date 17 March 2014.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants must have had transfusion-dependent anemia defined as having an average transfusion need of at least 2 units of packed red blood cells (pRBCs) per 28 days during the 112 days preceding randomization; No consecutive 56-day period that was RBC-transfusion-free during the 112 days preceding randomization; hemoglobin levels ≤ 9.5 g/dL

Reporting Groups
  Description
Placebo 3 placebo capsules by mouth (PO) daily (QD) for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent.
Lenalidomide

Lenalidomide 10 mg 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.


Participant Flow:   Overall Study
    Placebo   Lenalidomide
STARTED   79   160 
COMPLETED   1 [1]   15 [1] 
NOT COMPLETED   78   145 
Adverse Event                9                52 
Lack of therapeutic effect                56                69 
Withdrawal by Subject                10                16 
Protocol Violation                2                3 
Unspecified                1                5 
[1] Completed participants are those who were continuing to receive study drug at time of data cut-off



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Intent-to-Treat (ITT) population includes all participants who were randomized.

Reporting Groups
  Description
Placebo 3 placebo capsules by mouth (PO) daily (QD) for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent.
Lenalidomide

Lenalidomide 10 mg 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.

Total Total of all reporting groups

Baseline Measures
   Placebo   Lenalidomide   Total 
Overall Participants Analyzed 
[Units: Participants]
 79   160   239 
Age 
[Units: Years]
Mean (Standard Deviation)
 68.9  (8.26)   70.0  (8.19)   69.6  (8.21) 
Gender 
[Units: Participants]
     
Female   25   52   77 
Male   54   108   162 
Race/Ethnicity, Customized 
[Units: Participants]
     
Asian   1   1   2 
Black or African American   0   2   2 
White   69   133   202 
Japanese   4   8   12 
Other: Race Not disclosed   4   15   19 
Other   1   1   2 
Packed RBC (pRBC) transfusion burden [1] 
[Units: pRBC units]
Mean (Standard Deviation)
 3.4  (1.37)   3.4  (1.23)   3.4  (1.28) 
[1] The baseline transfusion burden is the number of units over 112 days by the randomization divided by 4. RBC transfusion burden (units/28 days): as a continuous variable, average of 28 days RBC transfusion units is based on all transfusion units within 112 days by the randomization date
International Prognostic Scoring System (IPSS) Investigator determined [1] 
[Units: Participants]
     
Low   30   85   115 
Intermediate 1   49   75   124 
[1] The Myelodysplastic Syndrome (MDS) IPSS score assesses the severity of MDS based on 3 prognostic factors each assigned a score: the percentage of bone marrow blasts, chromosome changes in the marrow cells (karyotype) and the presence of one or more low blood cell counts (cytopenias). The IPSS score is the sum of the bone marrow blast + karyotype + cytopenia score and ranges from 0 (low risk) to 3.5 (high risk). Prognosis is categorized as Low risk (score = 0), Intermediate-1 (score 0.5 to 1.0), Intermediate-2 (score 1.5 to 2.0) or High risk (score ≥ 2.5).
World Health Organization Classification 2008 of MDS by Central Review [1] 
[Units: Participants]
     
Refractory anemia (RA)   1   1   2 
Refractory cytopenia unilineage dysplasia (RCUD)   0   5   5 
RA with ringed sideroblasts (RARS)   7   12   19 
Refractory cytopenia multilineage dysplasia (RCMD)   59   115   174 
Refractory anemia with excess blasts-1 (RAEB-1)   12   27   39 
[1] The World Health Organization (WHO) 2008 classification recognizes eight subtypes of MDS that are distinguished by the percentage of myeloblasts, presence or absence of ringed sideroblasts (i.e., erythroid precursors with iron deposits surrounding the nucleus), presence of a monocytosis or a deletion 5q.
Prior Erythropoiesis-stimulating agent (ESA) Treatment [1] 
[Units: Participants]
     
Yes   63   125   188 
No   16   35   51 
[1] Erythropoiesis-stimulating agents (ESA) are similar to the cytokine (erythropoietin) that stimulates red blood cell production (erythropoieisis). ESAs, structurally and biologically, are similar to naturally occurring protein erythropoietin. ESAs are used to maintain hemoglobin at the lowest level that both minimizes transfusions and best meets a person's needs
Hemoglobin 
[Units: g/dL]
Mean (Standard Deviation)
 8.7  (1.37)   8.7  (1.23)   8.7  (1.28) 
Gene Expression Signature [1] 
[Units: Participants]
 3   14   17 
[1] A prespecified subgroup of participants with an erythroid differentiation gene expression signature predictive of lenalidomide response


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percentage of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence for ≥ 56 Days as Determined by an Independent Review Committee (IRC)   [ Time Frame: Up to 49 months; From randomization to the data cut-off of 17 Mar 2014; maximum exposure to study drug was 1158 days ]

2.  Primary:   Percentage of Participants With a Erythroid Gene Signature Who Achieved RBC Transfusion Independence for ≥ 56 Days as Determined by an Independent Review Committee (IRC)   [ Time Frame: Up to 49 months; Up to data cut-off of 17 Mar 2014; maximum exposure to study drug was 1158 days ]

3.  Secondary:   Percentage of Participants Who Achieved RBC Transfusion Independence With a Duration of ≥ 24 Weeks (168 Days) as Determined by the Sponsor   [ Time Frame: Up to 49 months; From randomization to the data cut-off of 17 Mar 2014; maximum exposure to study drug was 1158 days ]

4.  Secondary:   Kaplan Meier Estimates of Duration of 56-day RBC TI Response as Determined by the Sponsor   [ Time Frame: Up to 49 months; from randomization to data cut-off of 17 Mar 2014; maximum exposure to study drug was 1158 days ]

5.  Secondary:   Percentage of Participants Who Achieved an Erythroid Response Based on Modified International Working Group (IWG) 2006 Criteria   [ Time Frame: Up to 49 months; From Randomization to Data Cut-Off 17 March 2014; Maximum exposure on study drug was1158 days ]

6.  Secondary:   Time to 56-Day RBC-Transfusion-independent Response as Determined by the Sponsor   [ Time Frame: From the first dose of study drug to Day 56 ]

7.  Secondary:   Kaplan Meier Estimates for Progression to Acute Myeloid Leukemia (AML)   [ Time Frame: Up to 49 months; From Randomization to Data Cut-Off 17 March 2014; Maximum exposure to study drug was 1158 days ]

8.  Secondary:   Kaplan Meier Estimate for Overall Survival (OS)   [ Time Frame: Up to 49 months; From randomization to data cut-off of 17 Mar 2014; maximum exposure to study drug was 1158 days ]

9.  Secondary:   Number of Participants With Treatment Emergent Adverse Events (TEAE)   [ Time Frame: From the first dose of study drug through 28 days after discontinuation from the study treatment; up to data cut-off of 17 Mar 2014; maximum exposure to study drug was 1158 days ]

10.  Secondary:   Compliance Rates Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) From Baseline to Week 48   [ Time Frame: 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 ]

11.  Secondary:   Mean Change From Baseline in the EORTC QLQ-C30 Fatigue Domain at Week 12 and 24   [ Time Frame: Baseline and Week 12, ±3 days and Week 24, ±3 days ]

12.  Secondary:   Mean Change From Baseline in the EORTC QLQ-C30 Dyspnea Domain at Week 12 and 24   [ Time Frame: Baseline and Week 12, ±3 days and Week 24, ±3 days ]

13.  Secondary:   Mean Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain at Week 12 and 24   [ Time Frame: Baseline and Week 12, ±3 days and Week 24, ±3 days ]

14.  Secondary:   Mean Change From Baseline in the EORTC QLQ-C30 Global Health Status/Quality of Life (QOL) Domain at Week 12 and 24   [ Time Frame: Baseline and Week 12, ±3 days and Week 24, ±3 days ]

15.  Secondary:   Mean Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain at Week 12 and 24   [ Time Frame: Baseline and Week 12, ±3 days and Week 24, ±3 days ]

16.  Secondary:   Mean Change From Baseline in Fatigue Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24   [ Time Frame: Baseline, Week 12, ±3 days and Week 24, ±3 days ]

17.  Secondary:   Mean Change From Baseline in the Dyspnea Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24   [ Time Frame: Baseline, Week 12, ±3 days and Week 24, ±3 days ]

18.  Secondary:   Mean Change From Baseline in the Physical Functioning Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24   [ Time Frame: Baseline, Week 12, ±3 days and Week 24, ±3 days ]

19.  Secondary:   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   [ Time Frame: Baseline, Week 12, ±3 days and Week 24, ±3 days ]

20.  Secondary:   Mean Change From Baseline in the Emotional Functioning Domain Associated With the EORTC QLQ-C30 Scale at Weeks 12 and 24   [ Time Frame: Baseline, Week 12, ±3 days and Week 24, ±3 days ]

21.  Secondary:   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   [ Time Frame: Baseline, Week 12, ±3 days and Week 24, ±3 days ]

22.  Secondary:   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   [ Time Frame: Baseline, Week 12, ±3 days and Week 24, ±3 days ]

23.  Secondary:   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   [ Time Frame: Baseline, Week 12, ±3 days and Week 24, ±3 days ]

24.  Secondary:   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   [ Time Frame: Baseline, Week 12, ±3 days and Week 24, ±3 days ]

25.  Secondary:   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   [ Time Frame: Baseline, Week 12, ±3 days and Week 24, ±3 days ]

26.  Post-Hoc:   Percentage of Participants Who Achieved an Erythroid Response Based on Original IWG 2006 Criteria   [ Time Frame: Up to 49 months; from randomization to data cut-off of 17 Mar 2014; maximum exposure to study drug was 1158 days ]

27.  Secondary:   Healthcare Resource Utilization (HRU): Rate of Inpatient Hospitalizations, Concomitant Procedures/Surgeries and the Differences Between Treatment Arms   [ Time Frame: Up to 5 years ]
Results not yet reported.   Anticipated Reporting Date:   05/2017   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
  Hide More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Anne McClain, Senior Study Manager
Organization: Celgene Corporation
phone: 888-260-1588
e-mail: clinicaltrialdisclosure@celgene.com



Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT01029262     History of Changes
Other Study ID Numbers: CC-5013-MDS-005
Study First Received: December 8, 2009
Results First Received: May 8, 2015
Last Updated: May 25, 2016
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Austria: Federal Office for Safety in Health Care
Belgium: Federal Agency for Medicinal Products and Health Products
Canada: Health Canada
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Israel: Ministry of Health
Japan: Pharmaceuticals and Medical Devices Agency
Italy: The Italian Medicines Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Portugal: National Pharmacy and Medicines Institute
Spain: Spanish Agency of Medicines
Turkey: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency