Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The purpose of this study is to assess pharmacokinetic and pharmacodynamic characteristics of oral lenalidomide monotherapy administered to patients with Low- or Intermediate-1-risk Myelodysplastic Syndrome (MDS).
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 10 mg Lenalidomide | Experimental | Participants in the Pharmacokinetic Phase received a single 10 mg oral dose of lenalidomide on Day -7. 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. 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 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. |
|
| 15 mg Lenalidomide Non-del 5q | Experimental | Following the enrollment of the first 25 patients into the Monotherapy Phase, a second group of 15 patients with low- or intermediate-1-risk MDS not associated with a del 5q (non-del 5q) cytogenetic abnormality were enrolled to receive 15 mg of 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 15 mg lenalidomide 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lenalidomide | Drug | Lenalidomide 5-mg capsules for oral administration |
|
| Measure | Description | Time Frame |
|---|---|---|
| PK Phase: Area-under-the Concentration-time Curve (AUC0-24) for Lenalidomide | 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. | 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. |
| Monotherapy Phase: Area-under-the Concentration-time Curve (AUC0-5) for Lenalidomide | 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. | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| PK Phase: Maximum Plasma Concentration of Lenalidomide (Cmax) | The maximum observed plasma concentration (Cmax) of lenalidomide (its R- and S- enantiomers and the enantiomers combined) after a single dose on day -7. | 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. |
Not provided
Inclusion Criteria:
Must understand and voluntarily sign an informed consent form.
Age ≥18 years at the time of signing the informed consent form.
Must be able to adhere to the study visit schedule and other protocol requirements.
Documented diagnosis of MDS that meets International Prognostic Scoring System (IPSS) criteria for Low- to Intermediate-1-risk disease.
•Must have a diagnosis of low- or intermediate- risk MDS without a del 5q chromosomal abnormality (patients taking 15 mg starting dose only).
Must be able to provide adequate bone marrow (BM) aspirate and biopsy specimens for histopathological analysis and standard cytogenetic analysis during the screening procedure.
Red blood cell (RBC) transfusion-dependent anemia defined as having received ≥4 transfusions of RBCs within 56 days of randomization or symptomatic anemia (hemoglobin < 9.0 g/dl).
Failed prior treatment with recombinant human erythropoietin (rhu-EPO) (≥ 30,000 U/week x 6) or serum erythropoietin (EPO) concentration ≥500 mU/ml (hemoglobin < 9.0 g/dl).
Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse 1) for at least 28 days before starting study drug; 2) while participating in the study; and 3) for at least 28 days after discontinuation from the study. The two methods of reliable contraception must include one highly effective method (i.e. intrauterine device [IUD], hormonal [birth control pills, injections, or implants], tubal ligation, partner's vasectomy) and one additional effective (barrier) method (i.e. latex condom, diaphragm, cervical cap). FCBP must be referred to a qualified provider of contraceptive methods, if needed.
Exclusion Criteria:
Pregnant or lactating females.
Prior therapy with lenalidomide.
Proliferative white blood cell (WBC) ≥12,000/µL) chronic myelomonocytic leukemia (CMML).
MDS secondary to treatment with radiotherapy, chemotherapy, and/or immunotherapy for malignant or autoimmune diseases.
Any of the following lab abnormalities:
Prior ≥grade-2 National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) allergic reaction to thalidomide.
Prior desquamating (blistering) rash while taking thalidomide.
Patients with ≥grade-2 neuropathy.
Clinically significant anemia due to factors such as iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis or gastrointestinal bleeding.
Use of cytotoxic chemotherapeutic agents, erythropoietin, or experimental agents (agents that are not commercially available) for the treatment of MDS within 28 days of the first day of study drug treatment.
Prior history of malignancy other than MDS (except basal cell or squamous cell carcinoma or carcinoma in situ of the cervix or breast) unless the subject has been free of disease for ≥3 years.
Any serious medical condition or psychiatric illness that will prevent the patient from signing the informed consent form or will place the subject at unacceptable risk if he/she participates in the study.
Known human immunodeficiency virus (HIV-1) positivity.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Robert Knight, MD | Celgene Corporation | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| H. Lee Moffitt Cancer Center and Research Institute | Tampa | Florida | 33612 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22936658 | Result | Komrokji RS, Lancet JE, Swern AS, Chen N, Paleveda J, Lush R, Saba HI, List AF. Combined treatment with lenalidomide and epoetin alfa in lower-risk patients with myelodysplastic syndrome. Blood. 2012 Oct 25;120(17):3419-24. doi: 10.1182/blood-2012-03-415661. Epub 2012 Aug 30. |
Not provided
Not provided
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.
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.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 10 mg Non-del 5q | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Pharmacokinetic Phase |
|
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Recombinant human erythropoietin | Drug | Recombinant human erythropoietin (rhu-EPO) subcutaneous injection of 40,000 units. |
|
| Monotherapy Phase: Maximum Plasma Concentration of Lenalidomide (Cmax) | The Maximum observed plasma concentration (Cmax) of lenalidomide (its R- and S- enantiomers and the enantiomers combined) after multiple dosing for 14 days. | 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. |
| PK Phase: Terminal Half-life (t1/2) | 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). | 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. |
| PK Phase: Percent of Administered Lenalidomide Excreted Over 24 Hours After a Single, Oral Dose | 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. | On Day -7 at predose and over the intervals of 0-5, 5-8, 8-12, and 12-24 hours postdose. |
| Monotherapy Phase: Percent of Lenalidomide Excreted Over 5 Hours Post Day 14 Dose | 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. | On Day 14, at predose and over the interval of 0-5 hours postdose. |
| Time to Grade 4 Neutropenia or Thrombocytopenia | 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. | From the date of first dose until 30 days after the last dose (up to 1218 days) |
| Percentage of Participants With a Erythroid Response Across All Phases | 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). | Assessed every 28 days until study discontinuation (up to 1218 days). |
| Percentage of Participants Overall With Erythroid Response by Baseline Erythropoietin Level | 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. | Assessed every 28 days until study discontinuation (up to 1218 days) |
| Change From Baseline in Bone Marrow Cellularity and Correlation With Grade 4 Myelosuppression | 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. | Baseline and Week 16 |
| Marrow-infiltrating Lymphocyte (MIL) Number and Cytolytic Activity | Due to the low number of bone marrow samples collected this analysis was not performed. | Pre-Study and Week 16 |
| FG001 | 15 mg Non-del 5q | 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. |
| FG002 | 10 mg Del 5q | 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. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
| Monotherapy Phase |
|
|
| Combined Treatment Phase |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 10 mg Non-del 5q | 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. |
| BG001 | 15 mg Non-del 5q | 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. |
| BG002 | 10 mg Del 5q | 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. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Participants could select more than 1 race option. | Number | participants |
| |||||||||||||||
| Duration of MDS | Mean | Standard Deviation | years |
| |||||||||||||||
| International Prognostic Scoring System (IPSS) Score | The MDS IPSS score = sum of marrow blast + karyotype + cytopenia score. Score ranges from 0 (low risk) to 3.5 (high risk). | Number | participants |
| |||||||||||||||
| Eastern Cooperative Oncology Group (ECOG) Performance Status | 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. | Number | participants |
| |||||||||||||||
| French-American-British (FAB) classification of MDS | 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. | Number | participants |
| |||||||||||||||
| Serum erythropoietin level | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | PK Phase: Area-under-the Concentration-time Curve (AUC0-24) for Lenalidomide | 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. | All Pharmacokinetic Phase participants. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 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. |
|
|
| |||||||||||||||||||||||||
| Secondary | PK Phase: Maximum Plasma Concentration of Lenalidomide (Cmax) | The maximum observed plasma concentration (Cmax) of lenalidomide (its R- and S- enantiomers and the enantiomers combined) after a single dose on day -7. | All Pharmacokinetic Phase participants | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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. |
|
| ||||||||||||||||||||||||||
| Secondary | Monotherapy Phase: Maximum Plasma Concentration of Lenalidomide (Cmax) | The Maximum observed plasma concentration (Cmax) of lenalidomide (its R- and S- enantiomers and the enantiomers combined) after multiple dosing for 14 days. | Monotherapy Phase pharmacokinetic population. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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. |
|
| ||||||||||||||||||||||||||
| Secondary | PK Phase: Terminal Half-life (t1/2) | 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). | Pharmacokinetic Phase participants. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | 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. |
|
| ||||||||||||||||||||||||||
| Secondary | PK Phase: Percent of Administered Lenalidomide Excreted Over 24 Hours After a Single, Oral Dose | 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. | PK Phase participants for whom data was available. | Posted | Geometric Mean | Geometric Coefficient of Variation | percent of administered dose | On Day -7 at predose and over the intervals of 0-5, 5-8, 8-12, and 12-24 hours postdose. |
|
| ||||||||||||||||||||||||||
| Secondary | Monotherapy Phase: Percent of Lenalidomide Excreted Over 5 Hours Post Day 14 Dose | 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. | Monotherapy Phase Pharmacokinetic Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | percent of administered dose | On Day 14, at predose and over the interval of 0-5 hours postdose. |
|
| ||||||||||||||||||||||||||
| Secondary | Time to Grade 4 Neutropenia or Thrombocytopenia | 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. | 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. | Posted | Median | Full Range | days | From the date of first dose until 30 days after the last dose (up to 1218 days) |
| |||||||||||||||||||||||||||
| Secondary | Percentage of Participants With a Erythroid Response Across All Phases | 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). | 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. | Posted | Number | percentage of participants | Assessed every 28 days until study discontinuation (up to 1218 days). |
| ||||||||||||||||||||||||||||
| Secondary | Percentage of Participants Overall With Erythroid Response by Baseline Erythropoietin Level | 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. | Safety population. | Posted | Number | percentage of participants | Assessed every 28 days until study discontinuation (up to 1218 days) |
|
| |||||||||||||||||||||||||||
| Secondary | Change From Baseline in Bone Marrow Cellularity and Correlation With Grade 4 Myelosuppression | 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. | Unable to obtain sufficient bone marrow samples to perform analyses. | Posted | Baseline and Week 16 |
| ||||||||||||||||||||||||||||||
| Primary | Monotherapy Phase: Area-under-the Concentration-time Curve (AUC0-5) for Lenalidomide | 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. | Monotherapy Phase pharmacokinetic population | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 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. |
|
| ||||||||||||||||||||||||||
| Secondary | Marrow-infiltrating Lymphocyte (MIL) Number and Cytolytic Activity | Due to the low number of bone marrow samples collected this analysis was not performed. | Unable to obtain sufficient bone marrow samples to perform analyses | Posted | Pre-Study and Week 16 |
|
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.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 10 mg Lenalidomide | 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. | 10 | 24 | 24 | 24 | ||
| EG001 | 15 mg Lenalidomide | 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. | 5 | 15 | 15 | 15 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Asthenia | General disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Disease progression NOS | General disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Pneumonia NOS | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
| |
| Parotitis | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
| |
| Sepsis NOS | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
| |
| Cardiac failure congestive | Cardiac disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Costochondritis | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Pain in limb | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Transient ischemic attack | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Dyspnea NOS | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Gangrene NOS | Vascular disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Diarrhea NOS | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Vomiting NOS | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Transfusion reaction | Injury, poisoning and procedural complications | MedDRA (10.0) | Systematic Assessment |
| |
| Urinary retention | Renal and urinary disorders | MedDRA (10.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Leukopenia NOS | Blood and lymphatic system disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Anaemia NOS | Blood and lymphatic system disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Autoimmune haemolytic anaemia NOS | Blood and lymphatic system disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Diarrhoea NOS | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Abdominal pain NOS | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Vomiting NOS | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Loose stools | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Abdominal pain lower | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Barrett's oesophagus | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Rash NOS | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Urticaria NOS | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Contusion | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Dermatitis NOS | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Increased tendency to bruise | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Pruritus generalised | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Purpura NOS | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Swelling face | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Xeroderma | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Muscle cramp | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Pain in limb | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Peripheral swelling | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Bursa disorder | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Chest wall pain | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Intervertebral disc herniation | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Muscle tightness | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Osteoporosis NOS | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Sensation of heaviness | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Pain NOS | General disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Gait abnormal | General disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Dyspnoea NOS | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Nasopharyngitis | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Hoarseness | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Postnasal drip | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Upper respiratory tract infection NOS | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
| |
| Urinary tract infection NOS | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
| |
| Sinusitis NOS | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Tooth infection | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
| |
| Ear infection NOS | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
| |
| Localised infection | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
| |
| Body tinea | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
| |
| Gingival infection | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
| |
| Otitis externa NOS | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
| |
| Respiratory tract infection NOS | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
| |
| Vaginitis bacterial NOS | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Cerebral atrophy | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Cognitive disorder | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Sleep apnoea syndrome | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Haemosiderosis | Metabolism and nutrition disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Appetite decreased NOS | Metabolism and nutrition disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Haemochromatosis | Metabolism and nutrition disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA (10.0) | Systematic Assessment |
| |
| Blood in stool | Investigations | MedDRA (10.0) | Systematic Assessment |
| |
| Blood urine present | Investigations | MedDRA (10.0) | Systematic Assessment |
| |
| Computerised tomogram abnormal | Investigations | MedDRA (10.0) | Systematic Assessment |
| |
| Faecal occult blood positive | Investigations | MedDRA (10.0) | Systematic Assessment |
| |
| Prostatic specific antigen increased | Investigations | MedDRA (10.0) | Systematic Assessment |
| |
| Vitamin b12 decreased | Investigations | MedDRA (10.0) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Urinary frequency | Renal and urinary disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Azotaemia | Renal and urinary disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Urine flow decreased | Renal and urinary disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Cardiac discomfort | Cardiac disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Thrombosis | Vascular disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Pallor | Vascular disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Post procedural pain | Injury, poisoning and procedural complications | MedDRA (10.0) | Systematic Assessment |
| |
| Lacrimation increased | Eye disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Ovarian cyst | Reproductive system and breast disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Prostatitis | Reproductive system and breast disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Deafness NOS | Ear and labyrinth disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Acquired hypothyroidism | Endocrine disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Hypersensitivity NOS | Immune system disorders | MedDRA (10.0) | Systematic Assessment |
| |
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (10.0) | Systematic Assessment |
| |
| Squamous cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (10.0) | Systematic Assessment |
|
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Associate Director, Clinical Trials Disclosure | Celgene Corporation | 1-888-260-1599 | clinicaltrialdisclosure@celgene.com |
| ID | Term |
|---|---|
| D000077269 | Lenalidomide |
| ID | Term |
|---|---|
| D010797 | Phthalimides |
| D010795 | Phthalic Acids |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D010881 | Piperidones |
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D054833 | Isoindoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
Not provided
Not provided
| Withdrawal by Subject |
|
| Protocol Violation |
|
| Other |
|
| Protocol Violation |
|
| Other |
|
| Male |
|
| Hispanic |
|
| Other |
|
| Intermediate-1 (0.5-1.0) |
|
| 1 |
|
| 2 |
|
| Refractory anemia with ringed sideroblasts (RARS) |
|
| Refractory anemia with excess blasts (RAEB) |
|
| Refractory anemia with excess blasts -1 (RAEB-1) |
|
| Other |
|
| ≥ 500 mIU/mL |
|
| Missing |
|
|
|
|
|
|
|
|
| OG001 | 15 mg Non-del 5q | 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. |
| OG002 | 10 mg Del 5q | 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. |
|
|
|
|
|
|