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Trial record 23 of 881 for:    LENALIDOMIDE

A Pharmacokinetic And Pharmacodynamic Study Of Oral Lenalidomide (Revlimid) In Subjects With Low- Or Intermediate-1-Risk Myelodysplastic Syndromes

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ClinicalTrials.gov Identifier: NCT00910858
Recruitment Status : Completed
First Posted : June 1, 2009
Results First Posted : September 30, 2013
Last Update Posted : September 30, 2013
Sponsor:
Information provided by (Responsible Party):
Celgene ( Celgene Corporation )

Study Type Interventional
Study Design Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Low- or Intermediate-1-risk Myelodysplastic Syndrome (MDS)
Interventions Drug: Lenalidomide
Drug: Recombinant human erythropoietin
Enrollment 40
Recruitment Details A total of 40 participants were enrolled at 1 site in this study, with 12 participants enrolled in the Pharmacokinetic (PK) Phase of the study, 39 participants enrolled in the Monotherapy Phase of the study, and 23 participants enrolled in the Combined Treatment Phase of the study.
Pre-assignment Details The Monotherapy Phase included an initial group of 24 patients (11 from the PK Phase and 13 newly enrolled) who participated in the multiple-dose PK assessment and a second group of 15 patients (15 mg Non-del 5q) for whom no PK samples were taken. Erythroid nonresponders or responders who relapsed could participate in the Combined Treatment Phase.
Arm/Group Title 10 mg Non-del 5q 15 mg Non-del 5q 10 mg Del 5q
Hide Arm/Group Description

Participants with low- or intermediate-1-risk myelodysplastic syndromes (MDS) not associated with a deletion 5q (del 5q) cytogenetic abnormality received a single 10 mg oral dose of lenalidomide on Day -7 in the Pharmacokinetic Phase.

During the Monotherapy Phase participants received 10 mg oral lenalidomide once daily. Erythroid responders could continue lenalidomide monotherapy in the absence of limiting toxicity, disease progression, or erythroid failure.

After the completion of 16 weeks of lenalidomide monotherapy, in the Combined Treatment Phase participants who were erythroid nonresponders and erythroid responders who had developed an erythroid relapse continued treatment with 10 mg lenalidomide daily in conjunction with recombinant human erythropoietin (rhu EPO) 40,000 units administered weekly by subcutaneous injection for 8 weeks. Responding patients could continue combined treatment.

Participants with low- or intermediate-1-risk MDS not associated with a deletion 5q (del 5q) cytogenetic abnormality were enrolled directly into the Monotherapy Phase and received 15 mg oral lenalidomide once daily. Erythroid responders could continue lenalidomide monotherapy in the absence of limiting toxicity, disease progression, or erythroid failure.

After the completion of 16 weeks of lenalidomide monotherapy, in the Combined Treatment Phase participants who were erythroid nonresponders and erythroid responders who had developed an erythroid relapse continued treatment with 15 mg lenalidomide daily in conjunction with recombinant human erythropoietin (rhu EPO) 40,000 units administered weekly by subcutaneous injection for 8 weeks. Responding patients could continue combined treatment.

Participants with a deletion 5q (del 5q) cytogenetic abnormality received a single 10 mg oral dose of lenalidomide on Day -7 in the Pharmacokinetic Phase.

During the Monotherapy Phase participants received 10 mg oral lenalidomide once daily. Erythroid responders could continue lenalidomide monotherapy in the absence of limiting toxicity, disease progression, or erythroid failure.

After the completion of 16 weeks of lenalidomide monotherapy, in the Combined Treatment Phase participants who were erythroid nonresponders and erythroid responders who had developed an erythroid relapse continued treatment with 10 mg of lenalidomide daily in conjunction with recombinant human erythropoietin (rhu EPO) 40,000 units administered weekly by subcutaneous injection for 8 weeks. Responding patients could continue combined treatment.

Period Title: Pharmacokinetic Phase
Started 9 0 3
Completed 8 0 3
Not Completed 1 0 0
Reason Not Completed
Adverse Event             1             0             0
Period Title: Monotherapy Phase
Started 17 [1] 15 [2] 7 [3]
Safety Population 17 [4] 15 [4] 7 [4]
Pharmacokinetic Population 17 0 [5] 7
Completed 0 0 0
Not Completed 17 15 7
Reason Not Completed
Adverse Event             3             2             0
Lack of therapeutic effect             9             6             4
Withdrawal by Subject             1             3             1
Protocol Violation             1             0             0
Other             3             4             2
[1]
Includes 8 participants from the PK Phase and 9 newly enrolled participants.
[2]
All 15 participants were newly enrolled into the Monotherapy Phase.
[3]
Includes 3 participants from the PK Phase and 4 newly enrolled participants.
[4]
All patients who took at least 1 dose of study drug during Monotherapy or Combined Treatment Phase.
[5]
Patients in the 15 mg Non-del 5q group were not included in the pharmacokinetic assessment.
Period Title: Combined Treatment Phase
Started 9 [1] 10 [1] 4 [1]
Completed 0 0 0
Not Completed 9 10 4
Reason Not Completed
Lack of therapeutic effect             8             6             3
Withdrawal by Subject             0             2             0
Protocol Violation             1             0             0
Other             0             2             1
[1]
Patients who discontinued the Monotherapy Phase due to erythroid non-response or erythroid relapse.
Arm/Group Title 10 mg Non-del 5q 15 mg Non-del 5q 10 mg Del 5q Total
Hide Arm/Group Description

Participants with low- or intermediate-1-risk myelodysplastic syndromes (MDS) not associated with a deletion 5q (del 5q) cytogenetic abnormality received a single 10 mg oral dose of lenalidomide on Day -7 in the Pharmacokinetic Phase.

During the Monotherapy Phase participants received 10 mg oral lenalidomide once daily. Erythroid responders could continue lenalidomide monotherapy in the absence of limiting toxicity, disease progression, or erythroid failure.

After the completion of 16 weeks of lenalidomide monotherapy, in the Combined Treatment Phase participants who were erythroid nonresponders and erythroid responders who had developed an erythroid relapse continued treatment with 10 mg lenalidomide daily in conjunction with recombinant human erythropoietin (rhu EPO) 40,000 units administered weekly by subcutaneous injection for 8 weeks. Responding patients could continue combined treatment.

Participants with low- or intermediate-1-risk MDS not associated with a deletion 5q (del 5q) cytogenetic abnormality were enrolled directly into the Monotherapy Phase and received 15 mg oral lenalidomide once daily. Erythroid responders could continue lenalidomide monotherapy in the absence of limiting toxicity, disease progression, or erythroid failure.

After the completion of 16 weeks of lenalidomide monotherapy, in the Combined Treatment Phase participants who were erythroid nonresponders and erythroid responders who had developed an erythroid relapse continued treatment with 15 mg lenalidomide daily in conjunction with recombinant human erythropoietin (rhu EPO) 40,000 units administered weekly by subcutaneous injection for 8 weeks. Responding patients could continue combined treatment.

Participants with a deletion 5q (del 5q) cytogenetic abnormality received a single 10 mg oral dose of lenalidomide on Day -7 in the Pharmacokinetic Phase.

During the Monotherapy Phase participants received 10 mg oral lenalidomide once daily. Erythroid responders could continue lenalidomide monotherapy in the absence of limiting toxicity, disease progression, or erythroid failure.

After the completion of 16 weeks of lenalidomide monotherapy, in the Combined Treatment Phase participants who were erythroid nonresponders and erythroid responders who had developed an erythroid relapse continued treatment with 10 mg of lenalidomide daily in conjunction with recombinant human erythropoietin (rhu EPO) 40,000 units administered weekly by subcutaneous injection for 8 weeks. Responding patients could continue combined treatment.

Total of all reporting groups
Overall Number of Baseline Participants 17 15 7 39
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 17 participants 15 participants 7 participants 39 participants
67.8  (10.96) 73.4  (6.51) 72.6  (7.39) 70.8  (9.07)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17 participants 15 participants 7 participants 39 participants
Female
3
  17.6%
4
  26.7%
4
  57.1%
11
  28.2%
Male
14
  82.4%
11
  73.3%
3
  42.9%
28
  71.8%
Race/Ethnicity, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 17 participants 15 participants 7 participants 39 participants
White 17 13 7 37
Hispanic 1 1 0 2
Other 1 1 0 2
[1]
Measure Description: Participants could select more than 1 race option.
Duration of MDS  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 17 participants 15 participants 7 participants 39 participants
2.8  (2.28) 2.6  (2.22) 4.2  (4.74) 3.0  (2.81)
International Prognostic Scoring System (IPSS) Score   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 17 participants 15 participants 7 participants 39 participants
Low risk (0) 8 8 2 18
Intermediate-1 (0.5-1.0) 9 7 5 21
[1]
Measure Description: The MDS IPSS score = sum of marrow blast + karyotype + cytopenia score. Score ranges from 0 (low risk) to 3.5 (high risk).
Eastern Cooperative Oncology Group (ECOG) Performance Status   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 17 participants 15 participants 7 participants 39 participants
0 2 4 1 7
1 14 11 6 31
2 1 0 0 1
[1]
Measure Description: ECOG performance status: 0 = Fully active, no restrictions; 1 = Restricted but ambulatory and capable of light work; 2 = Ambulatory and capable of self-care but unable to work.
French-American-British (FAB) classification of MDS   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 17 participants 15 participants 7 participants 39 participants
Refractory anemia (RA) 6 7 2 15
Refractory anemia with ringed sideroblasts (RARS) 5 6 0 11
Refractory anemia with excess blasts (RAEB) 3 1 4 8
Refractory anemia with excess blasts -1 (RAEB-1) 0 1 0 1
Other 3 0 1 4
[1]
Measure Description: Refractory anemia: characterized by less than 5% primitive blood cells (myeloblasts) in the bone marrow and pathological abnormalities primarily seen in red cell precursors; RARS: distinguished by the presence of 15% or greater red cell precursors in the marrow being abnormal iron-stuffed cells called "ringed sideroblasts"; RAEB: characterized by 5-20% myeloblasts in the marrow; RAEB-1: characterized by 5% to 9% blasts in the bone marrow and less than 5% blasts in the blood.
Serum erythropoietin level  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 17 participants 15 participants 7 participants 39 participants
< 500 mIU/mL 9 4 2 15
≥ 500 mIU/mL 7 2 5 14
Missing 1 9 0 10
1.Primary Outcome
Title PK Phase: Area-under-the Concentration-time Curve (AUC0-24) for Lenalidomide
Hide Description Area under the plasma concentration-time curve from Time 0 to 24 hours post-dose for lenalidomide after a single dose, calculated using the log-linear trapezoidal method.
Time Frame On Day -7 blood samples were taken at predose (0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, and 24 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
All Pharmacokinetic Phase participants.
Arm/Group Title 10 mg Lenalidomide
Hide Arm/Group Description:
Participants received a single oral dose of 10 mg lenalidomide on Day -7.
Overall Number of Participants Analyzed 12
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
817
(30.5%)
2.Primary Outcome
Title Monotherapy Phase: Area-under-the Concentration-time Curve (AUC0-5) for Lenalidomide
Hide Description Area under the plasma concentration-time curve from Time 0 to 5 hours postdose for lenalidomide (its R- and S- enantiomers and the enantiomers combined) after multiple dosing for 14 days, calculated using the log-linear trapezoidal method.
Time Frame On Day 14 blood samples were taken at predose (0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, and 5 hours postdose.
Hide Outcome Measure Data
Hide Analysis Population Description
Monotherapy Phase pharmacokinetic population
Arm/Group Title 10 mg Lenalidomide
Hide Arm/Group Description:
During the Monotherapy Phase participants received 10 mg oral lenalidomide once daily.
Overall Number of Participants Analyzed 24
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
Total Lenalidomide
563
(32.5%)
S-Lenalidomide
315
(34.2%)
R-Lenalidomide
248
(30.6%)
3.Secondary Outcome
Title PK Phase: Maximum Plasma Concentration of Lenalidomide (Cmax)
Time Frame On Day -7 blood samples were taken at predose (0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, and 24 hours postdose.
Hide Outcome Measure Data
Hide Analysis Population Description
All Pharmacokinetic Phase participants
Arm/Group Title 10 mg Lenalidomide
Hide Arm/Group Description:
Participants received a single oral dose of 10 mg lenalidomide on Day -7.
Overall Number of Participants Analyzed 12
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Total Lenalidomide
179
(33.6%)
S-Lenalidomide
101
(34.9%)
R-Lenalidomide
78.3
(32.7%)
4.Secondary Outcome
Title Monotherapy Phase: Maximum Plasma Concentration of Lenalidomide (Cmax)
Time Frame On Day 14 blood samples were taken at predose (0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, and 5 hours postdose.
Hide Outcome Measure Data
Hide Analysis Population Description
Monotherapy Phase pharmacokinetic population.
Arm/Group Title 10 mg Lenalidomide
Hide Arm/Group Description:
During the Monotherapy Phase participants received 10 mg oral lenalidomide once daily.
Overall Number of Participants Analyzed 24
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Total Lenalidomide
185
(38.7%)
S-Lenalidomide
104
(39%)
R-Lenalidomide
80.7
(38.8%)
5.Secondary Outcome
Title PK Phase: Terminal Half-life (t1/2)
Hide Description The apparent terminal half-life is the time required for plasma concentration to decrease by 50% after pseudo-equilibrium of distribution has been reached, and calculated as the natural logarithm of 2 (0.693) / Apparent terminal rate constant (λz).
Time Frame On Day -7 blood samples were taken at predose (0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, and 24 hours postdose.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Phase participants.
Arm/Group Title 10 mg Lenalidomide
Hide Arm/Group Description:
Participants received a single oral dose of 10 mg lenalidomide on Day -7.
Overall Number of Participants Analyzed 12
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hours
Total Lenalidomide
3.72
(19.5%)
S-Lenalidomide
4.14
(29.0%)
R-Lenalidomide
3.58
(21.4%)
6.Secondary Outcome
Title PK Phase: Percent of Administered Lenalidomide Excreted Over 24 Hours After a Single, Oral Dose
Hide Description

Percent of the administered dose of lenalidomide excreted unchanged in urine over 24 hours postdose after a single dose on Day -7, calculated as:

(amount excreted unchanged in urine over 24 hours postdose / Dose) * 100.

The dose was 10 mg for total lenalidomide and 5 mg for the enantiomers.

Time Frame On Day -7 at predose and over the intervals of 0-5, 5-8, 8-12, and 12-24 hours postdose.
Hide Outcome Measure Data
Hide Analysis Population Description
PK Phase participants for whom data was available.
Arm/Group Title 10 mg Lenalidomide
Hide Arm/Group Description:
Participants received a single oral dose of 10 mg lenalidomide on Day -7.
Overall Number of Participants Analyzed 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: percent of administered dose
Total Lenalidomide
65.1
(13.5%)
S-Lenalidomide
67.9
(13.9%)
R-Lenalidomide
62.2
(14.0%)
7.Secondary Outcome
Title Monotherapy Phase: Percent of Lenalidomide Excreted Over 5 Hours Post Day 14 Dose
Hide Description

Percent of the administered lenalidomide dose excreted unchanged in urine over 5 hours postdose after multiple dosing for 14 days, calculated as:

(amount excreted unchanged in urine over the first 5 hours postdose / Dose) * 100.

The dose was 10 mg for total lenalidomide and 5 mg for the enantiomers.

Time Frame On Day 14, at predose and over the interval of 0-5 hours postdose.
Hide Outcome Measure Data
Hide Analysis Population Description
Monotherapy Phase Pharmacokinetic Population.
Arm/Group Title 10 mg Lenalidomide
Hide Arm/Group Description:
During the Monotherapy Phase participants received 10 mg oral lenalidomide once daily.
Overall Number of Participants Analyzed 24
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: percent of administered dose
Total Lenalidomide
34.0
(60.3%)
S-Lenalidomide
35.4
(59.0%)
R-Lenalidomide
32.5
(62.0%)
8.Secondary Outcome
Title Time to Grade 4 Neutropenia or Thrombocytopenia
Hide Description Time to the first event of grade 4 neutropenia or thrombocytopenia, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0, was calculated as date of first event - date of first dose + 1.
Time Frame From the date of first dose until 30 days after the last dose (up to 1218 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population, which comprised all enrolled patients who took at least 1 dose of study drug during the Monotherapy Phase or the Combined Treatment Phase.
Arm/Group Title Non-del 5q Del 5q
Hide Arm/Group Description:

Participants with low- or intermediate-1-risk myelodysplastic syndromes (MDS) not associated with a deletion 5q (del 5q) cytogenetic abnormality received 10 or 15 mg oral lenalidomide once daily. Erythroid responders could continue lenalidomide monotherapy in the absence of limiting toxicity, disease progression, or erythroid failure.

During the Combined Treatment Phase participants who were erythroid nonresponders and erythroid responders who had developed an erythroid relapse continued treatment with 10 mg lenalidomide daily in conjunction with recombinant human erythropoietin (rhu EPO) 40,000 units administered weekly by subcutaneous injection for 8 weeks. Responding patients could continue combined treatment.

Participants with a deletion 5q (del 5q) cytogenetic abnormality received 10 mg oral lenalidomide once daily in the Monotherapy Phase. Erythroid responders could continue lenalidomide monotherapy in the absence of limiting toxicity, disease progression, or erythroid failure.

During the Combined Treatment Phase participants who were erythroid nonresponders and erythroid responders who had developed an erythroid relapse continued treatment with 10 mg of lenalidomide daily in conjunction with recombinant human erythropoietin (rhu EPO) 40,000 units administered weekly by subcutaneous injection for 8 weeks. Responding patients could continue combined treatment.

Overall Number of Participants Analyzed 32 7
Median (Full Range)
Unit of Measure: days
Grade 4 Neutropenia
69.0
(11 to 168)
28.0
(17 to 36)
Grade 4 Thrombocytopenia
53.0
(22 to 141)
29.0
(22 to 36)
9.Secondary Outcome
Title Percentage of Participants With a Erythroid Response Across All Phases
Hide Description Erythroid response was categorized as either a major response or a minor response. A major response was defined as red blood cell (RBC) transfusion independence during any consecutive 56-day period and an increase in hemoglobin of at least 1.5 g/dL. A minor response was defined as a ≥ 50% or ≥ 4 unit decrease in RBC transfusions from pretreatment requirements (the number of RBC transfusions required over an 8-week period before the start of study drug treatment).
Time Frame Assessed every 28 days until study discontinuation (up to 1218 days).
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population, which comprised all enrolled patients who took at least 1 dose of study drug during the Monotherapy Phase or the Combined Treatment Phase.
Arm/Group Title 10 mg Non-del 5q 15 mg Non-del 5q 10 mg Del 5q
Hide Arm/Group Description:

Participants with low- or intermediate-1-risk myelodysplastic syndromes (MDS) not associated with a deletion 5q (del 5q) cytogenetic abnormality received a single 10 mg oral dose of lenalidomide on Day -7 in the Pharmacokinetic Phase.

During the Monotherapy Phase participants received 10 mg oral lenalidomide once daily. Erythroid responders could continue lenalidomide monotherapy in the absence of limiting toxicity, disease progression, or erythroid failure.

After the completion of 16 weeks of lenalidomide monotherapy, in the Combined Treatment Phase participants who were erythroid nonresponders and erythroid responders who had developed an erythroid relapse continued treatment with 10 mg lenalidomide daily in conjunction with recombinant human erythropoietin (rhu EPO) 40,000 units administered weekly by subcutaneous injection for 8 weeks. Responding patients could continue combined treatment.

Participants with low- or intermediate-1-risk MDS not associated with a deletion 5q (del 5q) cytogenetic abnormality were enrolled directly into the Monotherapy Phase and received 15 mg oral lenalidomide once daily. Erythroid responders could continue lenalidomide monotherapy in the absence of limiting toxicity, disease progression, or erythroid failure.

After the completion of 16 weeks of lenalidomide monotherapy, in the Combined Treatment Phase participants who were erythroid nonresponders and erythroid responders who had developed an erythroid relapse continued treatment with 15 mg lenalidomide daily in conjunction with recombinant human erythropoietin (rhu EPO) 40,000 units administered weekly by subcutaneous injection for 8 weeks. Responding patients could continue combined treatment.

Participants with a deletion 5q (del 5q) cytogenetic abnormality received a single 10 mg oral dose of lenalidomide on Day -7 in the Pharmacokinetic Phase.

During the Monotherapy Phase participants received 10 mg oral lenalidomide once daily. Erythroid responders could continue lenalidomide monotherapy in the absence of limiting toxicity, disease progression, or erythroid failure.

After the completion of 16 weeks of lenalidomide monotherapy, in the Combined Treatment Phase participants who were erythroid nonresponders and erythroid responders who had developed an erythroid relapse continued treatment with 10 mg of lenalidomide daily in conjunction with recombinant human erythropoietin (rhu EPO) 40,000 units administered weekly by subcutaneous injection for 8 weeks. Responding patients could continue combined treatment.

Overall Number of Participants Analyzed 17 15 7
Measure Type: Number
Unit of Measure: percentage of participants
Major response 17.6 40.0 85.7
Minor response 5.9 0 0
10.Secondary Outcome
Title Percentage of Participants Overall With Erythroid Response by Baseline Erythropoietin Level
Hide Description To evaluate the predictive value of pretreatment serum erythropoietin (EPO) concentration for erythroid response to lenalidomide, the percentage of erythroid responders versus non-responders were stratified by Baseline EPO levels (≤ 500 mIU/mL versus > 500 mIU/mL). Response includes participants with either a major or minor response.
Time Frame Assessed every 28 days until study discontinuation (up to 1218 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population.
Arm/Group Title Responders Non-responders Overall
Hide Arm/Group Description:
Participants with a erythroid response.
Participants who were not erythroid responders.
All participants in the Safety population.
Overall Number of Participants Analyzed 16 23 39
Measure Type: Number
Unit of Measure: percentage of participants
Baseline EPO ≤ 500 mIU/mL 62.5 47.8 53.8
Baseline EPO > 500 mIU/mL 37.5 39.1 38.5
11.Secondary Outcome
Title Change From Baseline in Bone Marrow Cellularity and Correlation With Grade 4 Myelosuppression
Hide Description Bone marrow cellularity is the volume ratio of hematopoietic stem cells and adipocytes (fat cells). Due to the small number of bone marrow samples, this analysis was not performed.
Time Frame Baseline and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Unable to obtain sufficient bone marrow samples to perform analyses.
Arm/Group Title Non-del 5q Del 5q
Hide Arm/Group Description:

Participants with low- or intermediate-1-risk myelodysplastic syndromes (MDS) not associated with a deletion 5q (del 5q) cytogenetic abnormality received 10 or 15 mg oral lenalidomide once daily. Erythroid responders could continue lenalidomide monotherapy in the absence of limiting toxicity, disease progression, or erythroid failure.

After the completion of 16 weeks of lenalidomide monotherapy, in the Combined Treatment Phase participants who were erythroid nonresponders and erythroid responders who had developed an erythroid relapse continued treatment with 10 mg lenalidomide daily in conjunction with recombinant human erythropoietin (rhu EPO) 40,000 units administered weekly by subcutaneous injection for 8 weeks. Responding patients could continue combined treatment.

Participants with a deletion 5q (del 5q) cytogenetic abnormality received 10 mg oral lenalidomide once daily in the Monotherapy Phase. Erythroid responders could continue lenalidomide monotherapy in the absence of limiting toxicity, disease progression, or erythroid failure.

After the completion of 16 weeks of lenalidomide monotherapy, in the Combined Treatment Phase participants who were erythroid nonresponders and erythroid responders who had developed an erythroid relapse continued treatment with 10 mg of lenalidomide daily in conjunction with recombinant human erythropoietin (rhu EPO) 40,000 units administered weekly by subcutaneous injection for 8 weeks. Responding patients could continue combined treatment.

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
12.Secondary Outcome
Title Marrow-infiltrating Lymphocyte (MIL) Number and Cytolytic Activity
Hide Description Due to the low number of bone marrow samples collected this analysis was not performed.
Time Frame Pre-Study and Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Unable to obtain sufficient bone marrow samples to perform analyses
Arm/Group Title Non-del 5q Del 5q
Hide Arm/Group Description:

Participants with low- or intermediate-1-risk myelodysplastic syndromes (MDS) not associated with a deletion 5q (del 5q) cytogenetic abnormality received 10 or 15 mg oral lenalidomide once daily. Erythroid responders could continue lenalidomide monotherapy in the absence of limiting toxicity, disease progression, or erythroid failure.

After the completion of 16 weeks of lenalidomide monotherapy, in the Combined Treatment Phase participants who were erythroid nonresponders and erythroid responders who had developed an erythroid relapse continued treatment with 10 mg lenalidomide daily in conjunction with recombinant human erythropoietin (rhu EPO) 40,000 units administered weekly by subcutaneous injection for 8 weeks. Responding patients could continue combined treatment.

Participants with a deletion 5q (del 5q) cytogenetic abnormality received 10 mg oral lenalidomide once daily in the Monotherapy Phase. Erythroid responders could continue lenalidomide monotherapy in the absence of limiting toxicity, disease progression, or erythroid failure.

After the completion of 16 weeks of lenalidomide monotherapy, in the Combined Treatment Phase participants who were erythroid nonresponders and erythroid responders who had developed an erythroid relapse continued treatment with 10 mg of lenalidomide daily in conjunction with recombinant human erythropoietin (rhu EPO) 40,000 units administered weekly by subcutaneous injection for 8 weeks. Responding patients could continue combined treatment.

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame The safety analyses were conducted on data collected from the time of first dose of study drug to 30 days after the last dose of study drug.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 10 mg Lenalidomide 15 mg Lenalidomide
Hide Arm/Group Description

Participants with low- or intermediate-1-risk myelodysplastic syndromes (MDS) received a single 10 mg oral dose of lenalidomide on Day -7 in the Pharmacokinetic Phase.

During the Monotherapy Phase participants received 10 mg oral lenalidomide once daily. Erythroid responders could continue lenalidomide monotherapy in the absence of limiting toxicity, disease progression, or erythroid failure.

After the completion of 16 weeks of lenalidomide monotherapy, in the Combined Treatment Phase participants who were erythroid nonresponders and erythroid responders who had developed an erythroid relapse continued treatment with 10 mg lenalidomide daily in conjunction with recombinant human erythropoietin (rhu EPO) 40,000 units administered weekly by subcutaneous injection for 8 weeks. Responding patients could continue combined treatment.

Participants with low- or intermediate-1-risk MDS were enrolled directly into the Monotherapy Phase and received 15 mg oral lenalidomide once daily. Erythroid responders could continue lenalidomide monotherapy in the absence of limiting toxicity, disease progression, or erythroid failure.

After the completion of 16 weeks of lenalidomide monotherapy, in the Combined Treatment Phase participants who were erythroid nonresponders and erythroid responders who had developed an erythroid relapse continued treatment with 15 mg lenalidomide daily in conjunction with recombinant human erythropoietin (rhu EPO) 40,000 units administered weekly by subcutaneous injection for 8 weeks. Responding patients could continue combined treatment.

All-Cause Mortality
10 mg Lenalidomide 15 mg Lenalidomide
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
10 mg Lenalidomide 15 mg Lenalidomide
Affected / at Risk (%) Affected / at Risk (%)
Total   10/24 (41.67%)   5/15 (33.33%) 
Cardiac disorders     
Cardiac failure congestive  1  1/24 (4.17%)  1/15 (6.67%) 
Myocardial infarction  1  1/24 (4.17%)  0/15 (0.00%) 
Gastrointestinal disorders     
Diarrhea NOS  1  1/24 (4.17%)  0/15 (0.00%) 
Nausea  1  1/24 (4.17%)  0/15 (0.00%) 
Vomiting NOS  1  1/24 (4.17%)  0/15 (0.00%) 
General disorders     
Asthenia  1  0/24 (0.00%)  1/15 (6.67%) 
Disease progression NOS  1  1/24 (4.17%)  0/15 (0.00%) 
Fatigue  1  1/24 (4.17%)  0/15 (0.00%) 
Infections and infestations     
Pneumonia NOS  1  1/24 (4.17%)  1/15 (6.67%) 
Parotitis  1  1/24 (4.17%)  0/15 (0.00%) 
Sepsis NOS  1  1/24 (4.17%)  0/15 (0.00%) 
Injury, poisoning and procedural complications     
Transfusion reaction  1  1/24 (4.17%)  0/15 (0.00%) 
Musculoskeletal and connective tissue disorders     
Costochondritis  1  1/24 (4.17%)  0/15 (0.00%) 
Pain in limb  1  1/24 (4.17%)  0/15 (0.00%) 
Nervous system disorders     
Dizziness  1  1/24 (4.17%)  0/15 (0.00%) 
Transient ischemic attack  1  1/24 (4.17%)  0/15 (0.00%) 
Renal and urinary disorders     
Urinary retention  1  0/24 (0.00%)  1/15 (6.67%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnea NOS  1  1/24 (4.17%)  0/15 (0.00%) 
Epistaxis  1  1/24 (4.17%)  0/15 (0.00%) 
Vascular disorders     
Deep vein thrombosis  1  0/24 (0.00%)  1/15 (6.67%) 
Gangrene NOS  1  1/24 (4.17%)  0/15 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (10.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
10 mg Lenalidomide 15 mg Lenalidomide
Affected / at Risk (%) Affected / at Risk (%)
Total   24/24 (100.00%)   15/15 (100.00%) 
Blood and lymphatic system disorders     
Neutropenia  1  22/24 (91.67%)  14/15 (93.33%) 
Leukopenia NOS  1  21/24 (87.50%)  12/15 (80.00%) 
Thrombocytopenia  1  21/24 (87.50%)  11/15 (73.33%) 
Anaemia NOS  1  17/24 (70.83%)  9/15 (60.00%) 
Autoimmune haemolytic anaemia NOS  1  0/24 (0.00%)  1/15 (6.67%) 
Cardiac disorders     
Palpitations  1  1/24 (4.17%)  1/15 (6.67%) 
Atrial fibrillation  1  0/24 (0.00%)  1/15 (6.67%) 
Cardiac discomfort  1  0/24 (0.00%)  1/15 (6.67%) 
Ear and labyrinth disorders     
Deafness NOS  1  0/24 (0.00%)  1/15 (6.67%) 
Endocrine disorders     
Acquired hypothyroidism  1  0/24 (0.00%)  1/15 (6.67%) 
Eye disorders     
Lacrimation increased  1  0/24 (0.00%)  1/15 (6.67%) 
Gastrointestinal disorders     
Diarrhoea NOS  1  10/24 (41.67%)  11/15 (73.33%) 
Constipation  1  5/24 (20.83%)  5/15 (33.33%) 
Abdominal pain NOS  1  2/24 (8.33%)  4/15 (26.67%) 
Abdominal pain upper  1  4/24 (16.67%)  2/15 (13.33%) 
Nausea  1  1/24 (4.17%)  4/15 (26.67%) 
Vomiting NOS  1  1/24 (4.17%)  4/15 (26.67%) 
Abdominal distension  1  2/24 (8.33%)  1/15 (6.67%) 
Loose stools  1  2/24 (8.33%)  0/15 (0.00%) 
Abdominal pain lower  1  0/24 (0.00%)  1/15 (6.67%) 
Barrett's oesophagus  1  0/24 (0.00%)  1/15 (6.67%) 
Dyspepsia  1  0/24 (0.00%)  1/15 (6.67%) 
Rectal haemorrhage  1  0/24 (0.00%)  1/15 (6.67%) 
Toothache  1  0/24 (0.00%)  1/15 (6.67%) 
General disorders     
Fatigue  1  6/24 (25.00%)  4/15 (26.67%) 
Pyrexia  1  6/24 (25.00%)  2/15 (13.33%) 
Asthenia  1  2/24 (8.33%)  3/15 (20.00%) 
Oedema peripheral  1  3/24 (12.50%)  2/15 (13.33%) 
Pain NOS  1  1/24 (4.17%)  1/15 (6.67%) 
Chest pain  1  0/24 (0.00%)  1/15 (6.67%) 
Gait abnormal  1  0/24 (0.00%)  1/15 (6.67%) 
Malaise  1  0/24 (0.00%)  1/15 (6.67%) 
Immune system disorders     
Hypersensitivity NOS  1  0/24 (0.00%)  1/15 (6.67%) 
Infections and infestations     
Upper respiratory tract infection NOS  1  5/24 (20.83%)  3/15 (20.00%) 
Urinary tract infection NOS  1  0/24 (0.00%)  4/15 (26.67%) 
Tooth infection  1  1/24 (4.17%)  2/15 (13.33%) 
Ear infection NOS  1  1/24 (4.17%)  1/15 (6.67%) 
Localised infection  1  1/24 (4.17%)  1/15 (6.67%) 
Body tinea  1  0/24 (0.00%)  1/15 (6.67%) 
Cellulitis  1  0/24 (0.00%)  1/15 (6.67%) 
Gingival infection  1  0/24 (0.00%)  1/15 (6.67%) 
Otitis externa NOS  1  0/24 (0.00%)  1/15 (6.67%) 
Respiratory tract infection NOS  1  0/24 (0.00%)  1/15 (6.67%) 
Vaginitis bacterial NOS  1  0/24 (0.00%)  1/15 (6.67%) 
Injury, poisoning and procedural complications     
Post procedural pain  1  0/24 (0.00%)  2/15 (13.33%) 
Investigations     
Weight decreased  1  1/24 (4.17%)  1/15 (6.67%) 
Blood in stool  1  0/24 (0.00%)  1/15 (6.67%) 
Blood urine present  1  0/24 (0.00%)  1/15 (6.67%) 
Computerised tomogram abnormal  1  0/24 (0.00%)  1/15 (6.67%) 
Faecal occult blood positive  1  0/24 (0.00%)  1/15 (6.67%) 
Prostatic specific antigen increased  1  0/24 (0.00%)  1/15 (6.67%) 
Vitamin b12 decreased  1  0/24 (0.00%)  1/15 (6.67%) 
Metabolism and nutrition disorders     
Haemosiderosis  1  0/24 (0.00%)  4/15 (26.67%) 
Appetite decreased NOS  1  1/24 (4.17%)  1/15 (6.67%) 
Haemochromatosis  1  1/24 (4.17%)  1/15 (6.67%) 
Hypomagnesaemia  1  0/24 (0.00%)  1/15 (6.67%) 
Musculoskeletal and connective tissue disorders     
Muscle cramp  1  7/24 (29.17%)  4/15 (26.67%) 
Back pain  1  1/24 (4.17%)  3/15 (20.00%) 
Neck pain  1  1/24 (4.17%)  1/15 (6.67%) 
Pain in limb  1  1/24 (4.17%)  1/15 (6.67%) 
Peripheral swelling  1  0/24 (0.00%)  2/15 (13.33%) 
Bursa disorder  1  0/24 (0.00%)  1/15 (6.67%) 
Chest wall pain  1  0/24 (0.00%)  1/15 (6.67%) 
Intervertebral disc herniation  1  0/24 (0.00%)  1/15 (6.67%) 
Muscle tightness  1  0/24 (0.00%)  1/15 (6.67%) 
Myalgia  1  0/24 (0.00%)  1/15 (6.67%) 
Osteoporosis NOS  1  0/24 (0.00%)  1/15 (6.67%) 
Sensation of heaviness  1  0/24 (0.00%)  1/15 (6.67%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal cell carcinoma  1  0/24 (0.00%)  1/15 (6.67%) 
Squamous cell carcinoma  1  0/24 (0.00%)  1/15 (6.67%) 
Nervous system disorders     
Headache  1  3/24 (12.50%)  2/15 (13.33%) 
Tremor  1  1/24 (4.17%)  1/15 (6.67%) 
Cerebral atrophy  1  0/24 (0.00%)  1/15 (6.67%) 
Cognitive disorder  1  0/24 (0.00%)  1/15 (6.67%) 
Hypoaesthesia  1  0/24 (0.00%)  1/15 (6.67%) 
Sleep apnoea syndrome  1  0/24 (0.00%)  1/15 (6.67%) 
Psychiatric disorders     
Insomnia  1  3/24 (12.50%)  3/15 (20.00%) 
Renal and urinary disorders     
Urinary frequency  1  0/24 (0.00%)  2/15 (13.33%) 
Azotaemia  1  0/24 (0.00%)  1/15 (6.67%) 
Nephrolithiasis  1  0/24 (0.00%)  1/15 (6.67%) 
Urine flow decreased  1  0/24 (0.00%)  1/15 (6.67%) 
Reproductive system and breast disorders     
Ovarian cyst  1  0/24 (0.00%)  1/15 (6.67%) 
Prostatitis  1  0/24 (0.00%)  1/15 (6.67%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  4/24 (16.67%)  7/15 (46.67%) 
Dyspnoea NOS  1  2/24 (8.33%)  5/15 (33.33%) 
Epistaxis  1  2/24 (8.33%)  1/15 (6.67%) 
Nasopharyngitis  1  1/24 (4.17%)  2/15 (13.33%) 
Dyspnoea exertional  1  0/24 (0.00%)  1/15 (6.67%) 
Hoarseness  1  0/24 (0.00%)  1/15 (6.67%) 
Postnasal drip  1  0/24 (0.00%)  1/15 (6.67%) 
Productive cough  1  0/24 (0.00%)  1/15 (6.67%) 
Rhinorrhoea  1  0/24 (0.00%)  1/15 (6.67%) 
Sinusitis NOS  1  3/24 (12.50%)  0/15 (0.00%) 
Skin and subcutaneous tissue disorders     
Pruritus  1  9/24 (37.50%)  7/15 (46.67%) 
Rash NOS  1  7/24 (29.17%)  2/15 (13.33%) 
Urticaria NOS  1  1/24 (4.17%)  3/15 (20.00%) 
Contusion  1  3/24 (12.50%)  0/15 (0.00%) 
Dermatitis NOS  1  1/24 (4.17%)  1/15 (6.67%) 
Increased tendency to bruise  1  1/24 (4.17%)  1/15 (6.67%) 
Night sweats  1  1/24 (4.17%)  1/15 (6.67%) 
Erythema  1  0/24 (0.00%)  1/15 (6.67%) 
Pruritus generalised  1  0/24 (0.00%)  1/15 (6.67%) 
Purpura NOS  1  0/24 (0.00%)  1/15 (6.67%) 
Swelling face  1  0/24 (0.00%)  1/15 (6.67%) 
Xeroderma  1  0/24 (0.00%)  1/15 (6.67%) 
Vascular disorders     
Thrombosis  1  1/24 (4.17%)  1/15 (6.67%) 
Pallor  1  0/24 (0.00%)  1/15 (6.67%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (10.0)
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.
  • Multicenter publication must include input from investigators and Celgene, agreement to be established before publication. It has priority over subset (single center) publication, for duration of 1 year after study completion.
  • Individual investigators have publication right after multicenter publication is complete (or 1 year after study completion), whichever is first. In this case, Celgene has the right to comment and right to ask delay of publication for 60 days.
Results Point of Contact
Name/Title: Associate Director, Clinical Trials Disclosure
Organization: Celgene Corporation
Phone: 1-888-260-1599
Responsible Party: Celgene ( Celgene Corporation )
ClinicalTrials.gov Identifier: NCT00910858     History of Changes
Obsolete Identifiers: NCT00360880
Other Study ID Numbers: CC-5013-PK-002
First Submitted: May 28, 2009
First Posted: June 1, 2009
Results First Submitted: July 31, 2013
Results First Posted: September 30, 2013
Last Update Posted: September 30, 2013