Lenalidomide Safety/Efficacy in Myelodysplastic Syndromes (MDS) Associated With a Deletion (Del)(5q) Cytogenetic Abnormality - Study Results

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Single Group Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	Myelodysplastic Syndromes
Intervention:	Drug: lenalidomide

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups

	Description
Lenalidomide	The protocol initially employed a syncopated dosage regimen in which 10 mg of lenalidomide was taken orally once daily on Days 1 to 21 of a 28-day cycle, but was subsequently amended to employ a continuous dosage regimen in which 10 mg of lenalidomide was taken without a planned rest period. Participants who initially began therapy on the syncopated regimen and who did not experience dose-limiting adverse events (AEs) were allowed to switch to the continuous regimen.

Description

Lenalidomide

The protocol initially employed a syncopated dosage regimen in which 10 mg of lenalidomide was taken orally once daily on Days 1 to 21 of a 28-day cycle, but was subsequently amended to employ a continuous dosage regimen in which 10 mg of lenalidomide was taken without a planned rest period. Participants who initially began therapy on the syncopated regimen and who did not experience dose-limiting adverse events (AEs) were allowed to switch to the continuous regimen.

Participant Flow: Overall Study

	Lenalidomide
STARTED	148
Modified Intent to Treat Population	94
COMPLETED	24 ^[1]
NOT COMPLETED	124
Adverse Event	37
Lack of Efficacy	52
Withdrawal by Subject	8
Lost to Follow-up	1
Death	11
Study Closed by Sponsor	2
Disease Progression	7
Investigator Decision	2
Non-Compliance	2
Loss of Response	1
Secondary Malign Disease	1

[1]	24 patients rolled over to free drug due to sponsor closure of study.

Baseline Characteristics

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Reporting Groups

	Description
Lenalidomide	The protocol initially employed a syncopated dosage regimen in which 10 mg of lenalidomide was taken orally once daily on Days 1 to 21 of a 28-day cycle, but was subsequently amended to employ a continuous dosage regimen in which 10 mg of lenalidomide was taken without a planned rest period. Participants who initially began therapy on the syncopated regimen and who did not experience dose-limiting adverse events (AEs) were allowed to switch to the continuous regimen.

Description

Lenalidomide

Baseline Measures

	Lenalidomide
Number of Participants [units: participants]	148
Age [units: years] Mean ± Standard Deviation	70.0 ± 10.50
Age, Customized [units: participants]
<= 65 years	48
>65 years	100
Gender [units: participants]
Female	97
Male	51
Race/Ethnicity, Customized [units: participants]
White	143
Hispanic	3
Asian/Pacific Islander	2
Region of Enrollment [units: participants]
United States	112
Germany	36
Duration of Myelodysplastic Syndrome (MDS) ^[1] [units: years] Mean ± Standard Deviation	3.4 ± 3.29
Participants with 5q(-) (31-33) Chromosomal Abnormality [units: participants]	148
International Prognostic Scoring System (IPSS) Score ^[2] [units: participants]
Low (0)	49
Intermediate-1 (0.5 to 1.0)	69
Intermediate-2 (1.5 to 2.0)	7
High (>=2.5)	2
Missing (unable to assign)	21
French-American-British (FAB) Classification ^[3] [units: participants]
Refractory anemia (RA)	78
Refractory anemia with ringed sideroblasts (RARS)	16
Refractory anemia with excess blasts (RAEB)	30
Chronic myelomonocytic leukemia (CMML)	3
Acute leukemia	1
Unable to classify	20
Cytogenetic Complexity [units: participants]
Isolated 5q	110
Intermediate (5q + 1 abnormality)	25
Complex	12
Unknown	1
Eastern Cooperative Oncology Group (ECOG) Performance Status ^[4] [units: participants]
0	59
1	75
2	14
3 - 5	0

[1]	Time from diagnosis of MDS until study start.
[2]	The international prognostic scoring system (IPSS) is a standard for risk assessment in primary myelodysplastic syndromes (MDS) that categorizes prognoses taking into account cytogenetics, cytopenias, blasts and blood counts. The IPSS prognostic subgroups consist of low-, intermediate-1-, intermediate-2-, and high-risk groups. The scale is 0-3.5 at 0.5 increments. Scores of 0=Low; 0.5-1.0=Int-1; 1.5-2.0=Int-2; 2.5-3.5=High risk which corresponds to poorer prognosis. The assessment was performed by the Central Reviewer.
[3]	FAB is a classification system for five (5) subtypes of myelodysplastic syndrome that are distinguished by the percentage of myeloblasts, presence or absence of ringed sideroblasts or a monocytosis. Classification was made by the Central Reviewer.
[4]	ECOG indicates a person's ability to perform life's functions on a scale of 0-5: 0= fully active and no restrictions restricted but ambulatory and capable of light work ambulatory and capable of self-care but unable to work 3-4= increasingly restricted 5= dead

Outcome Measures

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1. Primary:

Participants Who Achieved Red Blood Cell (RBC) -Transfusion Independence [ Time Frame: Up to 2 years ]

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2. Secondary:

Participants With Adverse Experiences [ Time Frame: Up to 2 Years ]

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3. Secondary:

Participants With a >= 50% Decrease From Baseline in Red Blood Cell (RBC) Transfusion Requirements Over Any Consecutive 56 Days During Study [ Time Frame: Baseline (Day -54 to Day 0), During study (Day 1 up to 2 years) ]

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4. Secondary:

Time to Transfusion Independence [ Time Frame: up to 2 years ]

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5. Secondary:

Participants Who Relapsed or Maintained Their Transfusion Independence After Achieving Transfusion Independence During the Study [ Time Frame: up to 2 years ]

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6. Secondary:

Kaplan Meier Estimate for Duration of Transfusion Independence Response [ Time Frame: up to 2 years ]

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7. Secondary:

Change in Hemoglobin Concentration From Baseline to Maximum Value During Response Period for Responders [ Time Frame: Baseline (Day -54 to Day 0), During study (Day 1 up to 2 years) ]

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8. Secondary:

Participant Counts of Cytogenetic Response [ Time Frame: up to 2 years ]

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9. Secondary:

Participant Counts of Platelet Response [ Time Frame: up to 2 years ]

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10. Secondary:

Participant Counts of Absolute Neutrophil Count (ANC) Response [ Time Frame: up to 2 years ]

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11. Secondary:

Participants With Complete or Partial Bone Marrow Improvement [ Time Frame: up to 2 years ]

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12. Secondary:

Participants With Bone Marrow Progression [ Time Frame: up to 2 years ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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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:

	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.
	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.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Unless approved by Celgene, single center data will not be published before multicenter data, unless more than 1 year has elapsed since completion of the Study. Thereafter, Investigator may publish single center data provided that Investigator shall: i) provide a copy of the publication to Celgene at least 60 days in advance of submission for publication; ii) delete Celgene Confidential Information and; iii) delay submission up to 90 additional days to permit intellectual property filings.

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
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Results Point of Contact:

Name/Title: Associate Director, Clinical Trials Disclosure
Organization: Celgene Corporation
phone: 1-888-260-1599
e-mail: clinicaltrialdisclosure@celgene.com

Publications of Results:

List A, Dewald G, Bennett J, Giagounidis A, Raza A, Feldman E, Powell B, Greenberg P, Thomas D, Stone R, Reeder C, Wride K, Patin J, Schmidt M, Zeldis J, Knight R; Myelodysplastic Syndrome-003 Study Investigators. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med. 2006 Oct 5;355(14):1456-65.

Responsible Party:	Celgene Corporation
ClinicalTrials.gov Identifier:	NCT00065156 History of Changes
Other Study ID Numbers:	CC-5013-MDS-003
Study First Received:	July 17, 2003
Results First Received:	August 31, 2009
Last Updated:	October 5, 2011
Health Authority:	United States: Food and Drug Administration