Anemia
Conditions
Keywords
Myelodysplastic Syndromes, MDS, transfusion dependent anemia, Erythropoiesis stimulating agents, non-del 5q
Brief summary
The purpose of this study is to investigate whether lenalidomide would reduce the number of red blood cell transfusions (RBC) needed in anemic (RBC transfusion-dependent) participants with low or intermediate-1 risk MDS without a deletion 5q chromosome abnormality. The study also investigated the safety of lenalidomide use in these participants. Two-thirds of the participants received oral lenalidomide and one-third of the participants received oral placebo.
Interventions
DRUGLenalidomide
One 10 mg Lenalidomide capsule + 2 placebo capsules or (3 placebo capsules) once daily for subjects with a creatinine clearance ≥ 60 mL/min. Alternatively-one 5 mg Lenalidomide capsule + 2 placebo capsules (or 3 placebo capsules) once daily for subjects with a creatinine clearance between 40 and 60 mL/min. Subjects may take study drug for at least 168 days unless there are intolerable side effects or disease progresses. Subjects may continue study drug beyond 168 days if they have an erythroid response (increase in their hemoglobin levels and fewer transfusions administered than before starting study drug)
OTHERPlacebo
3 placebo capsules once daily. Subjects may take study drug for at least 168 days unless there are intolerable side effects or disease progresses. Subjects may continue study drug beyond 168 days if they have an erythroid response (increase in their hemoglobin levels and fewer transfusions administered than before starting study drug)
Sponsors
Celgene
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years or older * Diagnosis of low or intermediate-1 risk Myelodysplastic (MDS) with any chromosome karyotype except del 5q\[31\] * Anemia that requires red blood cell transfusions * Resistant to erythropoiesis stimulating agents (ESAs) or blood erythropoietin level \> 500 mU/mL * Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 2 * Must agree to follow pregnancy precautions as required by the protocol. * Must agree to receive counseling related to teratogenic and other risks of lenalidomide * Must agree not to donate blood or semen * Must be willing to consent to two or more bone marrow aspirate procedures to be completed during study
Exclusion criteria
* Subjects previously receiving immunomodulating or immunosuppressive agents, or epigenetic or deoxyribonucleic acid (DNA) modulation agents * Allergic reaction to thalidomide * Renal insufficiency creatinine clearance (CrC1)\<40 mL/min by Cockcroft-Gault method) * Prior history of cancer, other than MDS, unless the subject has been free of the disease for ≥ 5 years. (Basal cell carcinoma of the skin, carcinoma in situ of the cervix, or stage Tumor (T) 1a or T1b prostate cancer is allowed) * Absolute neutrophil count (ANC) \< 500/uL * Platelets \< 50,000/uL * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 3X upper limit of normal * Uncontrolled hyperthyroidism or hypothyroidism * Significant neuropathy * Prior stem cell transplantation * Anemia due to reasons other than MDS * History of deep venous thrombosis (DVT) or pulmonary embolus (PE) within past 3 years * Significant active cardiac disease within the past 6 months * Known Human Immunodeficiency Virus (HIV) infection; known Hepatitis C infection or active Hepatitis B infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence for ≥ 56 Days as Determined by an Independent Review Committee (IRC) | From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively. | The percentage of participants who achieved the 56-day RBC transfusion independent (TI) response was defined as the absence of any RBC transfusions during any consecutive rolling 56-day interval within the double-blind treatment phase (ie, Days 2 (Day 1 is the first study drug day) to 57, Days 3 to 58, etcetera). The double-blind treatment phase was defined as the period between the 1st dosing up until 28 days after the last study drug dose |
| Percentage of Participants With a Erythroid Gene Signature Who Achieved RBC Transfusion Independence for ≥ 56 Days as Determined by an Independent Review Committee (IRC) | From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively. | The percentage of participants who achieved the 56-day RBC TI response was defined as the absence of any RBC transfusions during any consecutive rolling 56-day interval within the double-blind treatment phase (ie, Days 2 (Day 1 is the first study drug day) to 57, Days 3 to 58, etcetera). A participant who achieved at least a 56-day RBC-transfusion-independent response was considered a 56-day RBC-TI responder. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved an Erythroid Response Based on the Modified International Working Group (IWG) 2006 Criteria | From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively. | A participant was considered as having achieved an erythroid response if the participant either: \- had a hemoglobin (Hgb) increase ≥1.5 g/dL compared to baseline and confirmed by another central laboratory hemoglobin value at 4 to 8 weeks after the first Hgb measurement that also increased ≥1.5 g/dL. All Hgb values during this time interval must have had a ≥ 1.5 g/dL increase (ie, no central laboratory Hgb increase during this timeframe could be less \<1.5 g/dL) OR - had a 50% reduction in the number of the RBC transfusion units over any consecutive 56 days period compared to the baseline transfusion burden. The baseline transfusion burden is the number of units over 112 days by the randomization divided by 2. Only transfusions given for a pre-transfusion Hgb value of 9 g/dL or less were used in this response assessment. |
| Time to 56-Day RBC-Transfusion-Independent (TI) Response as Determined by the Sponsor | From first dose of study drug until 28 days after the last dose of study drug, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively. | The time to the first 56-day RBC-transfusion-independent response was calculated for participants who achieved a response. The day from the first dose of study drug to the date at which RBC-transfusion-independence starts was achieved and calculated using: Start date of the first response period - the date of the first study drug +1. A responder was defined as a participant who had a ≥ 56 consecutive days of RBC-transfusion-free period after the first dose of study drug in the treatment phase. |
| Kaplan Meier Estimates for Progression to Acute Myeloid Leukemia (AML) | From randomization to final data cut-off date of 03 Jul 2018; median follow up time for progression to AML was 2.3 years (range = 0 to 5.0 years) in the placebo arm and 2.6 years (range = 0 to 6.4 years) in the lenalidomide arm. | Progression to AML is part of the natural course of MDS and is a manifestation of disease progression. The time to progress to AML was calculated from the day of randomization to the first day when AML was diagnosed. Participants who died without AML were censored at the date of death. The participants who were lost to follow-up were censored at the last known day when participants did not have AML. Participants who did not progress to AML at the last follow-up contact were censored at the day of the last follow-up contact. |
| Kaplan Meier Estimate for Overall Survival (OS) | From randomization to final data cut-off date of 03 July 2018; maximum survival follow up was 6.4 years | Overall survival was assessed using the time between randomization and the date of death or date of censoring. Participants who were alive at a data cutoff date and participants who were lost to follow-up were censored at the last date when participants were known to be alive. |
| Number of Participants With Treatment Emergent Adverse Events (TEAE) | From the first dose of study drug through 28 days after discontinuation from the study treatment; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide arm and 529 days in the placebo arm. | A TEAE was defined as an AE that begins or worsens in intensity of frequency on or after the first dose of study drug through 28 days after last dose of study drug. A serious adverse event (SAE) is any: * Death; * Life-threatening event; * Any inpatient hospitalization or prolongation of existing hospitalization; * Persistent or significant disability or incapacity; * Congenital anomaly or birth defect; * Any other important medical event The investigator determined the relationship of an AE to study drug based on the timing of the AE relative to drug administration and whether or not other drugs, therapeutic interventions, or underlying conditions could provide a sufficient explanation for the event. The severity of an AE was evaluated by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (Version 3.0) where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death. |
| Compliance Rates Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) From Baseline to Week 48 | Baseline, Week 12, (±3 days), Week 24, (±3 days), Week 36, (±3 days), and Week 48 (±3 days); up to data cut-off of 17 Mar 2014 | The European Organization for Research and Treatment of Cancer QOL Questionnaire for Patients with Cancer (EORTC QLQ-C30) was a 30-item oncology-specific questionnaire. The questionnaire was developed to assess the quality of life of cancer patients. It contains 30 questions, 24 of which form 9 multi-item scales representing various aspects of HRQOL: 1 global scale, 5 functional scales (Physical, Role, Emotional, Cognitive and Social), and 3 symptom scales (Fatigue, Pain, and Nausea). The remaining 6 items are intended to be mono-item scales describing relevant cancer-oriented symptoms (dyspnea, insomnia, appetite, constipation, diarrhea, financial difficulties). Subscale scores are transformed to a 0 to 100 scale, with higher scores on functional scales indicating better function and higher score on symptom scales indicating worse symptoms. A participant was considered compliant at a visit if at least 15 out of the QLQ-C30 items in the questionnaire were checked. |
| Mean Change From Baseline in the EORTC QLQ-C30 Fatigue Domain at Week 12 and 24 | Baseline and Week 12, ±3 days and Week 24, ±3 days | The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate reduction in fatigue (i.e. improvement in symptom) and positive values indicate increases in fatigue (i.e. worsening of symptom). |
| Mean Change From Baseline in the EORTC QLQ-C30 Dyspnea Domain at Week 12 and 24 | Baseline and Week 12, ±3 days and Week 24, ±3 days | The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnea scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate decreased dyspnea (i.e. improvement in symptom) and positive values indicate increased dyspnea (i.e. worsening of symptom). |
| Mean Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain at Week 12 and 24 | Baseline and Week 12, ±3 days and Week 24, ±3 days | The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Physical Functioning Scale was scored between 0 and 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. |
| Mean Change From Baseline in the EORTC QLQ-C30 Global Health Status/Quality of Life (QOL) Domain at Week 12 and 24 | Baseline and Week 12, ±3 days and Week 24, ±3 days | The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status/QOL scale was scored between 0 and 100, with a high score indicating better Global Health Status/QOL. Negative change from Baseline values indicate deterioration in Global Health Status/QOL and positive values indicate improvement. |
| Mean Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain at Week 12 and 24 | Baseline and Week 12, ±3 days and Week 24, ±3 days | The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Emotional Functioning Domain was scored between 0 and 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. |
| Mean Change From Baseline in Fatigue Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24 | Baseline, Week 12, ±3 days and Week 24, ±3 days | The European Organization for Research and Treatment of Cancer QOL Questionnaire for Patients with Cancer (EORTC QLQ-C30) was a 30-item oncology-specific questionnaire. The questionnaire was developed to assess the quality of life of cancer patients. It contains 30 questions, 24 of which form 9 multi-item scales representing various aspects of HRQOL: 1 global scale, 5 functional scales (Physical, Role, Emotional, Cognitive and Social), and 3 symptom scales (Fatigue, Pain, and Nausea). The remaining 6 items are intended to be mono-item scales describing relevant cancer-oriented symptoms (dyspnea, insomnia, appetite, constipation, diarrhea, financial difficulties). The EORTC QLQ-C30 Fatigue Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate reduction in fatigue (i.e. improvement in symptom) and positive values indicate increases in fatigue (i.e. worsening of symptom). |
| Percentage of Participants Who Achieved RBC Transfusion Independence With a Duration of ≥ 24 Weeks (168 Days) as Determined by the Sponsor | From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively. | The 168-day RBC-transfusion-independent response was defined as the absence of any RBC transfusion during any consecutive rolling 168 days during the treatment period, for example Days 2 (Day 1 is the first study drug day) to 169, Days 3 to 170, Days 4 to 171, etcetera. A responder was defined as a participant who had a ≥ 168 consecutive days of RBC-transfusion-free period after the first dose of study drug in the treatment phase. |
| Mean Change From Baseline in the Physical Functioning Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24 | Baseline, Week 12, ±3 days and Week 24, ±3 days | The European Organization for Research and Treatment of Cancer QOL Questionnaire for Patients with Cancer (EORTC QLQ-C30) was a 30-item oncology-specific questionnaire. The questionnaire was developed to assess the quality of life of cancer patients. It contains 30 questions, 24 of which form 9 multi-item scales representing various aspects of HRQOL: 1 global scale, 5 functional scales (Physical, Role, Emotional, Cognitive and Social), and 3 symptom scales (Fatigue, Pain, and Nausea). The remaining 6 items are intended to be mono-item scales describing relevant cancer-oriented symptoms (dyspnea, insomnia, appetite, constipation, diarrhea, financial difficulties). The EORTC QLQ-C30 Physical Functioning was scored between 0 and 100, with a high score indicating better Global Health Status/QOL. Negative change from Baseline values indicate deterioration in Global Health Status/QOL and positive values indicate improvement. |
| Mean Change From Baseline in the Global Health Status/QoL Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24 | Baseline, Week 12, ±3 days and Week 24, ±3 days | The European Organization for Research and Treatment of Cancer QOL Questionnaire for Patients with Cancer (EORTC QLQ-C30) was a 30-item oncology-specific questionnaire. The questionnaire was developed to assess the quality of life of cancer patients. It contains 30 questions, 24 of which form 9 multi-item scales representing various aspects of HRQOL: 1 global scale, 5 functional scales (Physical, Role, Emotional, Cognitive and Social), and 3 symptom scales (Fatigue, Pain, and Nausea). The remaining 6 items are intended to be mono-item scales describing relevant cancer-oriented symptoms (dyspnea, insomnia, appetite, constipation, diarrhea, financial difficulties). The EORTC QLQ-C30 Global Health Status/QOL scale was scored between 0 and 100, with a high score indicating better Global Health Status/QOL. Negative change from Baseline values indicate deterioration in Global Health Status/QOL and positive values indicate improvement. |
| Mean Change From Baseline in the Emotional Functioning Domain Associated With the EORTC QLQ-C30 Scale at Weeks 12 and 24 | Baseline, Week 12, ±3 days and Week 24, ±3 days | The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Emotional Functioning Scale is scored between 0 and 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. |
| Percentage of Participants With a Clinically Meaningful Improvement in QOL (EORTC QLQ-C-30 Scale) From Baseline in Fatigue Domain at Weeks 12 and 24 | Baseline, Week 12, ±3 days and Week 24, ±3 days | The European Organization for Research and Treatment of Cancer QOL Questionnaire for Patients with Cancer (EORTC QLQ-C30) was a 30-item oncology-specific questionnaire. The questionnaire was developed to assess the quality of life of cancer patients. It contains 30 questions, 24 of which form 9 multi-item scales representing various aspects of HRQOL: 1 global scale, 5 functional scales (Physical, Role, Emotional, Cognitive and Social), and 3 symptom scales (Fatigue, Pain, and Nausea). The remaining 6 items are intended to be mono-item scales describing relevant cancer-oriented symptoms (dyspnea, insomnia, appetite, constipation, diarrhea, financial difficulties). Subscale scores are transformed to a 0 to 100 scale, with higher scores on functional scales indicating better function and higher score on symptom scales indicating worse symptoms. Improvement means at least 10 points better compared to baseline |
| Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline in the Dyspnea Domain at Weeks 12 and 24 | Baseline, Week 12, ±3 days and Week 24, ±3 days | The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnea scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate decreased dyspnea (i.e. improvement in symptom) and positive values indicate increased dyspnea (i.e. worsening of symptom). Improvement means at least 10 points better compared to baseline. |
| Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline Within the Physical Functioning Domain at Weeks 12 and 24 | Baseline, Week 12, ±3 days and Week 24, ±3 days | The European Organization for Research and Treatment of Cancer QOL Questionnaire for Patients with Cancer (EORTC QLQ-C30) was a 30-item oncology-specific questionnaire. The questionnaire was developed to assess the quality of life of cancer patients. It contains 30 questions, 24 of which form 9 multi-item scales representing various aspects of HRQOL: 1 global scale, 5 functional scales (Physical, Role, Emotional, Cognitive and Social), and 3 symptom scales (Fatigue, Pain, and Nausea). The remaining 6 items are intended to be mono-item scales describing relevant cancer-oriented symptoms (dyspnea, insomnia, appetite, constipation, diarrhea, financial difficulties). Subscale scores are transformed to a 0 to 100 scale, with higher scores on functional scales indicating better function and higher score on symptom scales indicating worse symptoms. A change of at least 10 points on the standardized domain scores was required for it to be considered clinically meaningful. |
| Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline in the Global Health Status/QOL Domain at Weeks 12 and 24 | Baseline, Week 12, ±3 days and Week 24, ±3 days | The European Organization for Research and Treatment of Cancer QOL Questionnaire for Patients with Cancer (EORTC QLQ-C30) was a 30-item oncology-specific questionnaire. The questionnaire was developed to assess the quality of life of cancer patients. It contains 30 questions, 24 of which form 9 multi-item scales representing various aspects of HRQOL: 1 global scale, 5 functional scales (Physical, Role, Emotional, Cognitive and Social), and 3 symptom scales (Fatigue, Pain, and Nausea). The remaining 6 items are intended to be mono-item scales describing relevant cancer-oriented symptoms (dyspnea, insomnia, appetite, constipation, diarrhea, financial difficulties). Subscale scores are transformed to a 0 to 100 scale, with higher scores on functional scales indicating better function and higher score on symptom scales indicating worse symptoms. A change of at least 10 points on the standardized domain scores was required for it to be considered clinically meaningful. |
| Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline in the Emotional Functioning Domain at Weeks 12 and 24 | Baseline, Week 12, ±3 days and Week 24, ±3 days | The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Emotional Functioning Domain was scored between 0 and 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. |
| Healthcare Resource Utilization (HRU): Rate of Inpatient Hospitalizations Related to Adverse Events Per Person Year | From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively. | Hospitalizations due to adverse events exclude those for transfusions, elective procedures or protocol-driven procedures. HRU was defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient. |
| Healthcare Resource Utilization (HRU): Duration of Hospitalizations Due to Adverse Events | From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively. | Hospitalizations due to adverse events exclude those for transfusions, elective procedures or protocol-driven procedures. HRU was defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient. |
| Healthcare Resource Utilization (HRU): Number of Days of Hospitalization Due to Adverse Events Per Person-Years | From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively. | Hospitalizations due to adverse events exclude those for transfusions, elective procedures or protocol-driven procedures. HRU was defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient |
| Mean Change From Baseline in the Dyspnea Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24 | Baseline, Week 12, ±3 days and Week 24, ±3 days | The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnea scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate decreased dyspnea (i.e. improvement in symptom) and positive values indicate increased dyspnea (i.e. worsening of symptom). |
| Kaplan Meier Estimates of Duration of 56-day RBC Transfusion Independence Response as Determined by the Sponsor | Response was assessed up to the end of treatment; up to the data cut-off date of 17 Mar 2014. | The duration of the first 56-day RBC transfusion-independence response was calculated for those who achieved a response and was dependent on whether a subsequent RBC transfusion was given after the transfusion-free period (response): * For those who received a subsequent RBC transfusion after the response starts, the duration of response was not censored, and was calculated as response duration = last day of response - first day of response +1 where the last day of response was defined as 1 day before the first RBC transfusion which was given at 56 days or more after the response starts. * For those who did not receive a subsequent RBC transfusion after the response started, the end day of the response was censored and duration of the response was calculated as response duration = date of last RBC transfusion assessment - first day of response+ 1. A responder was a participant who had a ≥ 56 consecutive days of RBC-transfusion-free period after the first study drug treatment period |
Countries
Australia, Austria, Belgium, Canada, Czechia, France, Germany, Israel, Italy, Japan, Poland, Portugal, Spain, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
239 participants were randomized at sites located in Europe (185), North America (24), Asia/Pacific (13) and the Middle East (17).
Pre-assignment details
Participants must have had transfusion-dependent anemia defined as having an average transfusion need of at least 2 units of packed red blood cells (pRBCs) per 28 days during the 112 days preceding randomization; No consecutive 56-day period that was RBC-transfusion-free during the 112 days preceding randomization; hemoglobin levels ≤ 9.5 g/dL.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received 3 placebo capsules by mouth daily for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent. | 79 |
| Lenalidomide Participants receieved lenalidomide 10 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 60 mL/min for at least 168 days until disease progression, intolerable side effects or withdrawal of consent.
Lenalidomide 5 mg PO daily plus 2 placebo capsules for participants with a creatinine clearance ≥ 40 and \< 60 mL/min. | 160 |
| Total | 239 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 9 | 52 |
| Overall Study | Death | 0 | 3 |
| Overall Study | Lack of therapeutic effect | 57 | 76 |
| Overall Study | Miscellaneous | 1 | 9 |
| Overall Study | Protocol Violation | 2 | 3 |
| Overall Study | Withdrawal by Subject | 10 | 17 |
Baseline characteristics
| Characteristic | Lenalidomide | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 70.0 years STANDARD_DEVIATION 8.19 | 68.9 years STANDARD_DEVIATION 8.26 | 69.6 years STANDARD_DEVIATION 8.21 |
| Gene Expression Signature | 14 Participants | 3 Participants | 17 Participants |
| Hemoglobin | 8.7 g/dL STANDARD_DEVIATION 1.23 | 8.7 g/dL STANDARD_DEVIATION 1.37 | 8.7 g/dL STANDARD_DEVIATION 1.28 |
| International Prognostic Scoring System (IPSS) Investigator Determined Intermediate 1 | 75 Participants | 49 Participants | 124 Participants |
| International Prognostic Scoring System (IPSS) Investigator Determined Low | 85 Participants | 30 Participants | 115 Participants |
| Packed RBC (pRBC) Transfusion Burden | 3.4 pRBC units/28 days STANDARD_DEVIATION 1.23 | 3.4 pRBC units/28 days STANDARD_DEVIATION 1.37 | 3.4 pRBC units/28 days STANDARD_DEVIATION 1.28 |
| Prior Erythropoiesis-stimulating Agent (ESA) Treatment No | 35 Participants | 16 Participants | 51 Participants |
| Prior Erythropoiesis-stimulating Agent (ESA) Treatment Yes | 125 Participants | 63 Participants | 188 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Japanese | 8 Participants | 4 Participants | 12 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Not Disclosed | 15 Participants | 4 Participants | 19 Participants |
| Race/Ethnicity, Customized White | 133 Participants | 69 Participants | 202 Participants |
| Sex: Female, Male Female | 52 Participants | 25 Participants | 77 Participants |
| Sex: Female, Male Male | 108 Participants | 54 Participants | 162 Participants |
| World Health Organization Classification 2008 of MDS by Central Review RA with ringed sideroblasts (RARS) | 12 Participants | 7 Participants | 19 Participants |
| World Health Organization Classification 2008 of MDS by Central Review Refractory anemia (RA) | 1 Participants | 1 Participants | 2 Participants |
| World Health Organization Classification 2008 of MDS by Central Review Refractory anemia with excess blasts-1 (RAEB-1) | 27 Participants | 12 Participants | 39 Participants |
| World Health Organization Classification 2008 of MDS by Central Review Refractory cytopenia multilineage dysplasia (RCMD) | 115 Participants | 59 Participants | 174 Participants |
| World Health Organization Classification 2008 of MDS by Central Review Refractory cytopenia unilineage dysplasia (RCUD) | 5 Participants | 0 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 43 / 79 | 94 / 160 |
| other Total, other adverse events | 70 / 79 | 154 / 160 |
| serious Total, serious adverse events | 16 / 79 | 62 / 160 |
Outcome results
Primary
Percentage of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence for ≥ 56 Days as Determined by an Independent Review Committee (IRC)
The percentage of participants who achieved the 56-day RBC transfusion independent (TI) response was defined as the absence of any RBC transfusions during any consecutive rolling 56-day interval within the double-blind treatment phase (ie, Days 2 (Day 1 is the first study drug day) to 57, Days 3 to 58, etcetera). The double-blind treatment phase was defined as the period between the 1st dosing up until 28 days after the last study drug dose
Time frame: From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.
Population: The Intent-to-Treat (ITT) population includes all participants who were randomized to either lenalidomide or placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence for ≥ 56 Days as Determined by an Independent Review Committee (IRC) | 2.5 percentage of participants |
| Lenalidomide | Percentage of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence for ≥ 56 Days as Determined by an Independent Review Committee (IRC) | 26.9 percentage of participants |
p-value: <0.00195% CI: [2.639, 42.702]Fisher Exact
Primary
Percentage of Participants With a Erythroid Gene Signature Who Achieved RBC Transfusion Independence for ≥ 56 Days as Determined by an Independent Review Committee (IRC)
The percentage of participants who achieved the 56-day RBC TI response was defined as the absence of any RBC transfusions during any consecutive rolling 56-day interval within the double-blind treatment phase (ie, Days 2 (Day 1 is the first study drug day) to 57, Days 3 to 58, etcetera). A participant who achieved at least a 56-day RBC-transfusion-independent response was considered a 56-day RBC-TI responder.
Time frame: From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.
Population: Analysis population includes ITT participants with an erythroid gene expression signature.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With a Erythroid Gene Signature Who Achieved RBC Transfusion Independence for ≥ 56 Days as Determined by an Independent Review Committee (IRC) | 0.0 percentage of participants |
| Lenalidomide | Percentage of Participants With a Erythroid Gene Signature Who Achieved RBC Transfusion Independence for ≥ 56 Days as Determined by an Independent Review Committee (IRC) | 7.1 percentage of participants |
p-value: 1Fisher Exact
Secondary
Compliance Rates Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) From Baseline to Week 48
The European Organization for Research and Treatment of Cancer QOL Questionnaire for Patients with Cancer (EORTC QLQ-C30) was a 30-item oncology-specific questionnaire. The questionnaire was developed to assess the quality of life of cancer patients. It contains 30 questions, 24 of which form 9 multi-item scales representing various aspects of HRQOL: 1 global scale, 5 functional scales (Physical, Role, Emotional, Cognitive and Social), and 3 symptom scales (Fatigue, Pain, and Nausea). The remaining 6 items are intended to be mono-item scales describing relevant cancer-oriented symptoms (dyspnea, insomnia, appetite, constipation, diarrhea, financial difficulties). Subscale scores are transformed to a 0 to 100 scale, with higher scores on functional scales indicating better function and higher score on symptom scales indicating worse symptoms. A participant was considered compliant at a visit if at least 15 out of the QLQ-C30 items in the questionnaire were checked.
Time frame: Baseline, Week 12, (±3 days), Week 24, (±3 days), Week 36, (±3 days), and Week 48 (±3 days); up to data cut-off of 17 Mar 2014
Population: Analyses were performed based on the Health Related Quality of Life (HRQoL) evaluable population, defined as all randomized participants who completed the baseline assessment and at least one post-baseline assessment for the intent to treat population. Data is available up to Week 48 due to small sample after that.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Compliance Rates Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) From Baseline to Week 48 | Week 12 | 78.5 percentage of participants |
| Placebo | Compliance Rates Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) From Baseline to Week 48 | Week 36 | 100 percentage of participants |
| Placebo | Compliance Rates Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) From Baseline to Week 48 | Week 24 | 80.6 percentage of participants |
| Placebo | Compliance Rates Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) From Baseline to Week 48 | Week 48 | 50 percentage of participants |
| Placebo | Compliance Rates Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) From Baseline to Week 48 | Baseline | 88.6 percentage of participants |
| Lenalidomide | Compliance Rates Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) From Baseline to Week 48 | Week 48 | 71.9 percentage of participants |
| Lenalidomide | Compliance Rates Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) From Baseline to Week 48 | Baseline | 90 percentage of participants |
| Lenalidomide | Compliance Rates Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) From Baseline to Week 48 | Week 12 | 83.8 percentage of participants |
| Lenalidomide | Compliance Rates Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) From Baseline to Week 48 | Week 24 | 85.8 percentage of participants |
| Lenalidomide | Compliance Rates Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) From Baseline to Week 48 | Week 36 | 80.5 percentage of participants |
Comparison: Baselinep-value: 0.823Fisher Exact
Comparison: Week 12 (±3 days)p-value: 0.371Fisher Exact
Comparison: Week 24 (±3 days)p-value: 0.391Fisher Exact
Comparison: Week 36 (±3 days)p-value: 1Fisher Exact
Comparison: Week 48 (±3 days)p-value: 0.508Fisher Exact
Secondary
Healthcare Resource Utilization (HRU): Duration of Hospitalizations Due to Adverse Events
Hospitalizations due to adverse events exclude those for transfusions, elective procedures or protocol-driven procedures. HRU was defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient.
Time frame: From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.
Population: Participants with at least one hospitalization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Healthcare Resource Utilization (HRU): Duration of Hospitalizations Due to Adverse Events | 9.0 Days |
| Lenalidomide | Healthcare Resource Utilization (HRU): Duration of Hospitalizations Due to Adverse Events | 11.0 Days |
Secondary
Healthcare Resource Utilization (HRU): Number of Days of Hospitalization Due to Adverse Events Per Person-Years
Hospitalizations due to adverse events exclude those for transfusions, elective procedures or protocol-driven procedures. HRU was defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient
Time frame: From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.
Population: Safety population includes all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Healthcare Resource Utilization (HRU): Number of Days of Hospitalization Due to Adverse Events Per Person-Years | 6.37 Days per person-years |
| Lenalidomide | Healthcare Resource Utilization (HRU): Number of Days of Hospitalization Due to Adverse Events Per Person-Years | 8.92 Days per person-years |
Secondary
Healthcare Resource Utilization (HRU): Rate of Inpatient Hospitalizations Related to Adverse Events Per Person Year
Hospitalizations due to adverse events exclude those for transfusions, elective procedures or protocol-driven procedures. HRU was defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient.
Time frame: From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.
Population: Safety population includes all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Healthcare Resource Utilization (HRU): Rate of Inpatient Hospitalizations Related to Adverse Events Per Person Year | 0.47 Hospitalizations per person-years |
| Lenalidomide | Healthcare Resource Utilization (HRU): Rate of Inpatient Hospitalizations Related to Adverse Events Per Person Year | 0.77 Hospitalizations per person-years |
Secondary
Kaplan Meier Estimate for Overall Survival (OS)
Overall survival was assessed using the time between randomization and the date of death or date of censoring. Participants who were alive at a data cutoff date and participants who were lost to follow-up were censored at the last date when participants were known to be alive.
Time frame: From randomization to final data cut-off date of 03 July 2018; maximum survival follow up was 6.4 years
Population: The ITT population includes all participants who were randomized to either lenalidomide or placebo.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Kaplan Meier Estimate for Overall Survival (OS) | 3.0 years |
| Lenalidomide | Kaplan Meier Estimate for Overall Survival (OS) | 3.8 years |
p-value: 0.98Log Rank
Secondary
Kaplan Meier Estimates for Progression to Acute Myeloid Leukemia (AML)
Progression to AML is part of the natural course of MDS and is a manifestation of disease progression. The time to progress to AML was calculated from the day of randomization to the first day when AML was diagnosed. Participants who died without AML were censored at the date of death. The participants who were lost to follow-up were censored at the last known day when participants did not have AML. Participants who did not progress to AML at the last follow-up contact were censored at the day of the last follow-up contact.
Time frame: From randomization to final data cut-off date of 03 Jul 2018; median follow up time for progression to AML was 2.3 years (range = 0 to 5.0 years) in the placebo arm and 2.6 years (range = 0 to 6.4 years) in the lenalidomide arm.
Population: ITT population includes all participants who were randomized and received either lenalidomide or placebo. One participant in the placebo arm was diagnosed as having AML before enrollment and was excluded from all analyses of progression to AML.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Kaplan Meier Estimates for Progression to Acute Myeloid Leukemia (AML) | NA years |
| Lenalidomide | Kaplan Meier Estimates for Progression to Acute Myeloid Leukemia (AML) | NA years |
p-value: 0.864Log Rank
Secondary
Kaplan Meier Estimates of Duration of 56-day RBC Transfusion Independence Response as Determined by the Sponsor
The duration of the first 56-day RBC transfusion-independence response was calculated for those who achieved a response and was dependent on whether a subsequent RBC transfusion was given after the transfusion-free period (response): * For those who received a subsequent RBC transfusion after the response starts, the duration of response was not censored, and was calculated as response duration = last day of response - first day of response +1 where the last day of response was defined as 1 day before the first RBC transfusion which was given at 56 days or more after the response starts. * For those who did not receive a subsequent RBC transfusion after the response started, the end day of the response was censored and duration of the response was calculated as response duration = date of last RBC transfusion assessment - first day of response+ 1. A responder was a participant who had a ≥ 56 consecutive days of RBC-transfusion-free period after the first study drug treatment period
Time frame: Response was assessed up to the end of treatment; up to the data cut-off date of 17 Mar 2014.
Population: The analysis was conducted only for those participants who achieved a 56-day transfusion independence response according to the sponsor's assessment. Responders in the intent to treat population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Kaplan Meier Estimates of Duration of 56-day RBC Transfusion Independence Response as Determined by the Sponsor | NA weeks |
| Lenalidomide | Kaplan Meier Estimates of Duration of 56-day RBC Transfusion Independence Response as Determined by the Sponsor | 30.9 weeks |
p-value: 0.639Log Rank
Secondary
Mean Change From Baseline in Fatigue Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24
The European Organization for Research and Treatment of Cancer QOL Questionnaire for Patients with Cancer (EORTC QLQ-C30) was a 30-item oncology-specific questionnaire. The questionnaire was developed to assess the quality of life of cancer patients. It contains 30 questions, 24 of which form 9 multi-item scales representing various aspects of HRQOL: 1 global scale, 5 functional scales (Physical, Role, Emotional, Cognitive and Social), and 3 symptom scales (Fatigue, Pain, and Nausea). The remaining 6 items are intended to be mono-item scales describing relevant cancer-oriented symptoms (dyspnea, insomnia, appetite, constipation, diarrhea, financial difficulties). The EORTC QLQ-C30 Fatigue Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate reduction in fatigue (i.e. improvement in symptom) and positive values indicate increases in fatigue (i.e. worsening of symptom).
Time frame: Baseline, Week 12, ±3 days and Week 24, ±3 days
Population: Analyses were performed based on the HRQoL evaluable population, defined as all randomized participants who completed the baseline assessment and at least one post-baseline assessment for the intent to treat population. Only those with available data at baseline and each time point are included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Fatigue Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24 | Week 24 | 7.376 units on a scale |
| Placebo | Mean Change From Baseline in Fatigue Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24 | Week 12 | -0.464 units on a scale |
| Lenalidomide | Mean Change From Baseline in Fatigue Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24 | Week 12 | 3.497 units on a scale |
| Lenalidomide | Mean Change From Baseline in Fatigue Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24 | Week 24 | 0.196 units on a scale |
Comparison: Week 12p-value: 0.2909t-test, 2 sided
Comparison: Week 24p-value: 0.0759t-test, 2 sided
Secondary
Mean Change From Baseline in the Dyspnea Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnea scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate decreased dyspnea (i.e. improvement in symptom) and positive values indicate increased dyspnea (i.e. worsening of symptom).
Time frame: Baseline, Week 12, ±3 days and Week 24, ±3 days
Population: Analyses were performed based on the HRQoL evaluable population, defined as all randomized participants who completed the baseline assessment and at least one post-baseline assessment for the intent to treat population. Only those with available data at baseline and each time point are included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Mean Change From Baseline in the Dyspnea Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24 | Week 12 | 1.696 units on a scale |
| Placebo | Mean Change From Baseline in the Dyspnea Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24 | Week 24 | 5.998 units on a scale |
| Lenalidomide | Mean Change From Baseline in the Dyspnea Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24 | Week 12 | 3.374 units on a scale |
| Lenalidomide | Mean Change From Baseline in the Dyspnea Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24 | Week 24 | -0.206 units on a scale |
Comparison: Week 12p-value: 0.6957t-test, 2 sided
Comparison: Week 24p-value: 0.1729t-test, 2 sided
Secondary
Mean Change From Baseline in the Emotional Functioning Domain Associated With the EORTC QLQ-C30 Scale at Weeks 12 and 24
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Emotional Functioning Scale is scored between 0 and 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
Time frame: Baseline, Week 12, ±3 days and Week 24, ±3 days
Population: Analyses were performed based on the HRQoL evaluable population, defined as all randomized participants who completed the baseline assessment and at least one post-baseline assessment for the intent to treat population. Only those with available data at baseline and each time point are included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Mean Change From Baseline in the Emotional Functioning Domain Associated With the EORTC QLQ-C30 Scale at Weeks 12 and 24 | Week 12 | 1.458 units on a scale |
| Placebo | Mean Change From Baseline in the Emotional Functioning Domain Associated With the EORTC QLQ-C30 Scale at Weeks 12 and 24 | Week 24 | -6.746 units on a scale |
| Lenalidomide | Mean Change From Baseline in the Emotional Functioning Domain Associated With the EORTC QLQ-C30 Scale at Weeks 12 and 24 | Week 12 | -1.876 units on a scale |
| Lenalidomide | Mean Change From Baseline in the Emotional Functioning Domain Associated With the EORTC QLQ-C30 Scale at Weeks 12 and 24 | Week 24 | -1.129 units on a scale |
Comparison: Week 12p-value: 0.2848t-test, 2 sided
Comparison: Week 24p-value: 0.1053t-test, 1 sided
Secondary
Mean Change From Baseline in the EORTC QLQ-C30 Dyspnea Domain at Week 12 and 24
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnea scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate decreased dyspnea (i.e. improvement in symptom) and positive values indicate increased dyspnea (i.e. worsening of symptom).
Time frame: Baseline and Week 12, ±3 days and Week 24, ±3 days
Population: Analyses were performed based on the Health Related Quality of Life (HRQoL) evaluable population, defined as all randomized participants who completed the baseline assessment and at least one post-baseline assessment for the intent to treat population. Only those with available data at baseline and each time point are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change From Baseline in the EORTC QLQ-C30 Dyspnea Domain at Week 12 and 24 | Week 12 | 0.6 units on a scale | Standard Deviation 28.06 |
| Placebo | Mean Change From Baseline in the EORTC QLQ-C30 Dyspnea Domain at Week 12 and 24 | Week 24 | 4.3 units on a scale | Standard Deviation 26.57 |
| Lenalidomide | Mean Change From Baseline in the EORTC QLQ-C30 Dyspnea Domain at Week 12 and 24 | Week 12 | 2.2 units on a scale | Standard Deviation 29.92 |
| Lenalidomide | Mean Change From Baseline in the EORTC QLQ-C30 Dyspnea Domain at Week 12 and 24 | Week 24 | 1.2 units on a scale | Standard Deviation 26.26 |
Comparison: Week 12p-value: 0.76ANOVA
Comparison: Week 24p-value: 0.251ANOVA
Secondary
Mean Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain at Week 12 and 24
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Emotional Functioning Domain was scored between 0 and 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
Time frame: Baseline and Week 12, ±3 days and Week 24, ±3 days
Population: Analyses were performed based on the HRQoL evaluable population, defined as all randomized participants who completed the baseline assessment and at least one post-baseline assessment for the intent to treat population. Only those with available data at baseline and each time point are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain at Week 12 and 24 | Week 12 | 1.2 units on a scale | Standard Deviation 18.7 |
| Placebo | Mean Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain at Week 12 and 24 | Week 24 | -7.1 units on a scale | Standard Deviation 20.78 |
| Lenalidomide | Mean Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain at Week 12 and 24 | Week 12 | -1.4 units on a scale | Standard Deviation 22.39 |
| Lenalidomide | Mean Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain at Week 12 and 24 | Week 24 | 0.8 units on a scale | Standard Deviation 20.06 |
Comparison: Week 12p-value: 0.265ANOVA
Comparison: Week 24p-value: 0.047ANOVA
Secondary
Mean Change From Baseline in the EORTC QLQ-C30 Fatigue Domain at Week 12 and 24
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate reduction in fatigue (i.e. improvement in symptom) and positive values indicate increases in fatigue (i.e. worsening of symptom).
Time frame: Baseline and Week 12, ±3 days and Week 24, ±3 days
Population: Analyses were performed based on the HRQoL evaluable population, defined as all randomized participants who completed the baseline assessment and at least one post-baseline assessment for the intent to treat population. Only those with available data at baseline and each time point are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change From Baseline in the EORTC QLQ-C30 Fatigue Domain at Week 12 and 24 | Week 12 | 0.6 units on a scale | Standard Deviation 17.53 |
| Placebo | Mean Change From Baseline in the EORTC QLQ-C30 Fatigue Domain at Week 12 and 24 | Week 24 | 7.6 units on a scale | Standard Deviation 20.74 |
| Lenalidomide | Mean Change From Baseline in the EORTC QLQ-C30 Fatigue Domain at Week 12 and 24 | Week 12 | 2.4 units on a scale | Standard Deviation 28.26 |
| Lenalidomide | Mean Change From Baseline in the EORTC QLQ-C30 Fatigue Domain at Week 12 and 24 | Week 24 | -1.5 units on a scale | Standard Deviation 26.42 |
Comparison: Week 12p-value: 0.323ANOVA
Comparison: Week 24p-value: 0.071ANOVA
Secondary
Mean Change From Baseline in the EORTC QLQ-C30 Global Health Status/Quality of Life (QOL) Domain at Week 12 and 24
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status/QOL scale was scored between 0 and 100, with a high score indicating better Global Health Status/QOL. Negative change from Baseline values indicate deterioration in Global Health Status/QOL and positive values indicate improvement.
Time frame: Baseline and Week 12, ±3 days and Week 24, ±3 days
Population: Analyses were performed based on the HRQoL evaluable population, defined as all randomized participants who completed the baseline assessment and at least one post-baseline assessment for the intent to treat population. Only those with available data at baseline and each time point are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change From Baseline in the EORTC QLQ-C30 Global Health Status/Quality of Life (QOL) Domain at Week 12 and 24 | Week 12 | -2.1 units on a scale | Standard Deviation 20.18 |
| Placebo | Mean Change From Baseline in the EORTC QLQ-C30 Global Health Status/Quality of Life (QOL) Domain at Week 12 and 24 | Week 24 | -4.1 units on a scale | Standard Deviation 20.25 |
| Lenalidomide | Mean Change From Baseline in the EORTC QLQ-C30 Global Health Status/Quality of Life (QOL) Domain at Week 12 and 24 | Week 12 | -1.4 units on a scale | Standard Deviation 24.35 |
| Lenalidomide | Mean Change From Baseline in the EORTC QLQ-C30 Global Health Status/Quality of Life (QOL) Domain at Week 12 and 24 | Week 24 | -2.4 units on a scale | Standard Deviation 27.87 |
Comparison: Week 12p-value: 0.746ANOVA
p-value: 0.46ANOVA
Secondary
Mean Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain at Week 12 and 24
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Physical Functioning Scale was scored between 0 and 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
Time frame: Baseline and Week 12, ±3 days and Week 24, ±3 days
Population: Analyses were performed based on the Health Related Quality of Life (HRQoL) evaluable population, defined as all randomized participants who completed the baseline assessment and at least one post-baseline assessment for the intent to treat population. Only those with available data at baseline and each time point are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain at Week 12 and 24 | Week 12 | -1.4 units on a scale | Standard Deviation 15.76 |
| Placebo | Mean Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain at Week 12 and 24 | Week 24 | -5.7 units on a scale | Standard Deviation 14.84 |
| Lenalidomide | Mean Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain at Week 12 and 24 | Week 12 | -2.1 units on a scale | Standard Deviation 18.09 |
| Lenalidomide | Mean Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain at Week 12 and 24 | Week 24 | -0.4 units on a scale | Standard Deviation 18.19 |
Comparison: Week 12p-value: 0.424ANOVA
Comparison: Week 24p-value: 0.116ANOVA
Secondary
Mean Change From Baseline in the Global Health Status/QoL Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24
The European Organization for Research and Treatment of Cancer QOL Questionnaire for Patients with Cancer (EORTC QLQ-C30) was a 30-item oncology-specific questionnaire. The questionnaire was developed to assess the quality of life of cancer patients. It contains 30 questions, 24 of which form 9 multi-item scales representing various aspects of HRQOL: 1 global scale, 5 functional scales (Physical, Role, Emotional, Cognitive and Social), and 3 symptom scales (Fatigue, Pain, and Nausea). The remaining 6 items are intended to be mono-item scales describing relevant cancer-oriented symptoms (dyspnea, insomnia, appetite, constipation, diarrhea, financial difficulties). The EORTC QLQ-C30 Global Health Status/QOL scale was scored between 0 and 100, with a high score indicating better Global Health Status/QOL. Negative change from Baseline values indicate deterioration in Global Health Status/QOL and positive values indicate improvement.
Time frame: Baseline, Week 12, ±3 days and Week 24, ±3 days
Population: Analyses were performed based on the HRQoL evaluable population, defined as all randomized participants who completed the baseline assessment and at least one post-baseline assessment for the intent to treat population. Only those with available data at baseline and each time point are included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Mean Change From Baseline in the Global Health Status/QoL Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24 | Week 12 | -1.201 units on a scale |
| Placebo | Mean Change From Baseline in the Global Health Status/QoL Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24 | Week 24 | -4.502 units on a scale |
| Lenalidomide | Mean Change From Baseline in the Global Health Status/QoL Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24 | Week 12 | -2.690 units on a scale |
| Lenalidomide | Mean Change From Baseline in the Global Health Status/QoL Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24 | Week 24 | -2.441 units on a scale |
Comparison: Week 12p-value: 0.6408t-test, 2 sided
Comparison: Week 24p-value: 0.575t-test, 2 sided
Secondary
Mean Change From Baseline in the Physical Functioning Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24
The European Organization for Research and Treatment of Cancer QOL Questionnaire for Patients with Cancer (EORTC QLQ-C30) was a 30-item oncology-specific questionnaire. The questionnaire was developed to assess the quality of life of cancer patients. It contains 30 questions, 24 of which form 9 multi-item scales representing various aspects of HRQOL: 1 global scale, 5 functional scales (Physical, Role, Emotional, Cognitive and Social), and 3 symptom scales (Fatigue, Pain, and Nausea). The remaining 6 items are intended to be mono-item scales describing relevant cancer-oriented symptoms (dyspnea, insomnia, appetite, constipation, diarrhea, financial difficulties). The EORTC QLQ-C30 Physical Functioning was scored between 0 and 100, with a high score indicating better Global Health Status/QOL. Negative change from Baseline values indicate deterioration in Global Health Status/QOL and positive values indicate improvement.
Time frame: Baseline, Week 12, ±3 days and Week 24, ±3 days
Population: Analyses were performed based on the HRQoL evaluable population, defined as all randomized participants who completed the baseline assessment and at least one post-baseline assessment for the intent to treat population. Only those with available data at baseline and each time point are included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Mean Change From Baseline in the Physical Functioning Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24 | Week 12 | 0.732 units on a scale |
| Placebo | Mean Change From Baseline in the Physical Functioning Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24 | Week 24 | -5.451 units on a scale |
| Lenalidomide | Mean Change From Baseline in the Physical Functioning Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24 | Week 12 | -2.919 units on a scale |
| Lenalidomide | Mean Change From Baseline in the Physical Functioning Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24 | Week 24 | -1.484 units on a scale |
Comparison: Week 12p-value: 0.3975t-test, 2 sided
Comparison: Week 24p-value: 0.1714t-test, 2 sided
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAE)
A TEAE was defined as an AE that begins or worsens in intensity of frequency on or after the first dose of study drug through 28 days after last dose of study drug. A serious adverse event (SAE) is any: * Death; * Life-threatening event; * Any inpatient hospitalization or prolongation of existing hospitalization; * Persistent or significant disability or incapacity; * Congenital anomaly or birth defect; * Any other important medical event The investigator determined the relationship of an AE to study drug based on the timing of the AE relative to drug administration and whether or not other drugs, therapeutic interventions, or underlying conditions could provide a sufficient explanation for the event. The severity of an AE was evaluated by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (Version 3.0) where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death.
Time frame: From the first dose of study drug through 28 days after discontinuation from the study treatment; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide arm and 529 days in the placebo arm.
Population: Safety population includes all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥ 1 GR 3-4 TEAE Leading to Stopping of Study Med | 6 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAE) | At least 1 TEAE | 74 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥ 1 Treatment Related AE (TEAE) | 42 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥ 1 Treatment related TEAE Causing Discontinuation | 3 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥ 1 TEAE Leading to Dose Reduction | 1 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥ 1 TEAE Leading to Dose Interruption | 11 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥ 1 TEAE Leading to Dose Interruption & Reduction | 5 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥ 1 TEAE Leading to Discontinuation of Study Drug | 9 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥ 1 Serious TEAE | 16 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥1 Treatment-Related Serious TEAE | 3 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥1 Serious TEAE Leading to Dose Reduction | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥1 serious TEAE leading to dose interruption | 4 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥1 SAE Causing Dose Interruption & reduction | 1 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥1 Serious TEAE Leading to Stopping of Study Drug | 4 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥1 Grade (GR) 3-4 TEAE | 35 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥ 1 GR 3-4 Related TEAE | 16 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥ 1 GR 3-4 Leading to Dose Reduction | 1 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥ 1 GR 3-4 TEAE Leading to Dose Interruption | 9 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥ 1 GR 3-4 TEAE dose Interruption &reduction | 4 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥ 1 GR 5 TEAE | 2 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥1 GR Treatment Related 5 TEAE | 1 Participants |
| Lenalidomide | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥ 1 TEAE Leading to Dose Reduction | 10 Participants |
| Lenalidomide | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥1 SAE Causing Dose Interruption & reduction | 3 Participants |
| Lenalidomide | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥1 GR Treatment Related 5 TEAE | 3 Participants |
| Lenalidomide | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥1 Serious TEAE Leading to Dose Reduction | 1 Participants |
| Lenalidomide | Number of Participants With Treatment Emergent Adverse Events (TEAE) | At least 1 TEAE | 160 Participants |
| Lenalidomide | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥ 1 GR 3-4 Related TEAE | 127 Participants |
| Lenalidomide | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥ 1 Treatment Related AE (TEAE) | 144 Participants |
| Lenalidomide | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥1 serious TEAE leading to dose interruption | 21 Participants |
| Lenalidomide | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥ 1 Treatment related TEAE Causing Discontinuation | 40 Participants |
| Lenalidomide | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥ 1 GR 5 TEAE | 6 Participants |
| Lenalidomide | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥ 1 GR 3-4 Leading to Dose Reduction | 8 Participants |
| Lenalidomide | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥ 1 TEAE Leading to Dose Interruption | 89 Participants |
| Lenalidomide | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥1 Serious TEAE Leading to Stopping of Study Drug | 24 Participants |
| Lenalidomide | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥ 1 TEAE Leading to Dose Interruption & Reduction | 68 Participants |
| Lenalidomide | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥ 1 GR 3-4 TEAE Leading to Stopping of Study Med | 41 Participants |
| Lenalidomide | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥ 1 TEAE Leading to Discontinuation of Study Drug | 51 Participants |
| Lenalidomide | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥1 Grade (GR) 3-4 TEAE | 139 Participants |
| Lenalidomide | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥ 1 Serious TEAE | 62 Participants |
| Lenalidomide | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥ 1 GR 3-4 TEAE Leading to Dose Interruption | 80 Participants |
| Lenalidomide | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥ 1 GR 3-4 TEAE dose Interruption &reduction | 64 Participants |
| Lenalidomide | Number of Participants With Treatment Emergent Adverse Events (TEAE) | ≥1 Treatment-Related Serious TEAE | 25 Participants |
Secondary
Percentage of Participants Who Achieved an Erythroid Response Based on the Modified International Working Group (IWG) 2006 Criteria
A participant was considered as having achieved an erythroid response if the participant either: \- had a hemoglobin (Hgb) increase ≥1.5 g/dL compared to baseline and confirmed by another central laboratory hemoglobin value at 4 to 8 weeks after the first Hgb measurement that also increased ≥1.5 g/dL. All Hgb values during this time interval must have had a ≥ 1.5 g/dL increase (ie, no central laboratory Hgb increase during this timeframe could be less \<1.5 g/dL) OR - had a 50% reduction in the number of the RBC transfusion units over any consecutive 56 days period compared to the baseline transfusion burden. The baseline transfusion burden is the number of units over 112 days by the randomization divided by 2. Only transfusions given for a pre-transfusion Hgb value of 9 g/dL or less were used in this response assessment.
Time frame: From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.
Population: The ITT population includes all participants who were randomized to either lenalidomide or placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved an Erythroid Response Based on the Modified International Working Group (IWG) 2006 Criteria | 30.4 percentage of participants |
| Lenalidomide | Percentage of Participants Who Achieved an Erythroid Response Based on the Modified International Working Group (IWG) 2006 Criteria | 38.8 percentage of participants |
p-value: 0.25295% CI: [0.867, 1.877]Fisher Exact
Secondary
Percentage of Participants Who Achieved RBC Transfusion Independence With a Duration of ≥ 24 Weeks (168 Days) as Determined by the Sponsor
The 168-day RBC-transfusion-independent response was defined as the absence of any RBC transfusion during any consecutive rolling 168 days during the treatment period, for example Days 2 (Day 1 is the first study drug day) to 169, Days 3 to 170, Days 4 to 171, etcetera. A responder was defined as a participant who had a ≥ 168 consecutive days of RBC-transfusion-free period after the first dose of study drug in the treatment phase.
Time frame: From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.
Population: The ITT population includes all participants who were randomized to either lenalidomide or placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved RBC Transfusion Independence With a Duration of ≥ 24 Weeks (168 Days) as Determined by the Sponsor | 0.0 percentage of participants |
| Lenalidomide | Percentage of Participants Who Achieved RBC Transfusion Independence With a Duration of ≥ 24 Weeks (168 Days) as Determined by the Sponsor | 17.5 percentage of participants |
p-value: <0.001Fisher Exact
Secondary
Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline in the Dyspnea Domain at Weeks 12 and 24
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnea scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate decreased dyspnea (i.e. improvement in symptom) and positive values indicate increased dyspnea (i.e. worsening of symptom). Improvement means at least 10 points better compared to baseline.
Time frame: Baseline, Week 12, ±3 days and Week 24, ±3 days
Population: Analyses were performed based on the HRQoL evaluable population, defined as all randomized participants who completed the baseline assessment and at least one post-baseline assessment for the intent to treat population. Only those with available data at baseline and each time point are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline in the Dyspnea Domain at Weeks 12 and 24 | Week 12 | 19.6 percentage of participants |
| Placebo | Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline in the Dyspnea Domain at Weeks 12 and 24 | Week 24 | 12.8 percentage of participants |
| Lenalidomide | Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline in the Dyspnea Domain at Weeks 12 and 24 | Week 12 | 21.3 percentage of participants |
| Lenalidomide | Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline in the Dyspnea Domain at Weeks 12 and 24 | Week 24 | 20.5 percentage of participants |
Comparison: Week 12p-value: 0.825Fisher Exact
Comparison: Week 24p-value: 0.568Fisher Exact
Secondary
Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline in the Emotional Functioning Domain at Weeks 12 and 24
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Emotional Functioning Domain was scored between 0 and 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
Time frame: Baseline, Week 12, ±3 days and Week 24, ±3 days
Population: Analyses were performed based on the HRQoL evaluable population, defined as all randomized participants who completed the baseline assessment and at least one post-baseline assessment for the intent to treat population. Only those with available data at baseline and each time point are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline in the Emotional Functioning Domain at Weeks 12 and 24 | Week 12 | 25.0 percentage of participants |
| Placebo | Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline in the Emotional Functioning Domain at Weeks 12 and 24 | Week 24 | 17.0 percentage of participants |
| Lenalidomide | Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline in the Emotional Functioning Domain at Weeks 12 and 24 | Week 12 | 20.5 percentage of participants |
| Lenalidomide | Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline in the Emotional Functioning Domain at Weeks 12 and 24 | Week 24 | 21.7 percentage of participants |
Comparison: Week 12p-value: 0.476Fisher Exact
Comparison: Week 24p-value: 0.052Fisher Exact
Secondary
Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline in the Global Health Status/QOL Domain at Weeks 12 and 24
The European Organization for Research and Treatment of Cancer QOL Questionnaire for Patients with Cancer (EORTC QLQ-C30) was a 30-item oncology-specific questionnaire. The questionnaire was developed to assess the quality of life of cancer patients. It contains 30 questions, 24 of which form 9 multi-item scales representing various aspects of HRQOL: 1 global scale, 5 functional scales (Physical, Role, Emotional, Cognitive and Social), and 3 symptom scales (Fatigue, Pain, and Nausea). The remaining 6 items are intended to be mono-item scales describing relevant cancer-oriented symptoms (dyspnea, insomnia, appetite, constipation, diarrhea, financial difficulties). Subscale scores are transformed to a 0 to 100 scale, with higher scores on functional scales indicating better function and higher score on symptom scales indicating worse symptoms. A change of at least 10 points on the standardized domain scores was required for it to be considered clinically meaningful.
Time frame: Baseline, Week 12, ±3 days and Week 24, ±3 days
Population: Analyses were performed based on the HRQoL evaluable population, defined as all randomized participants who completed the baseline assessment and at least one post-baseline assessment with the EORTC QLQ-C-30. Only those with available data at baseline and each time point are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline in the Global Health Status/QOL Domain at Weeks 12 and 24 | Week 12 | 19.6 percentage of participants |
| Placebo | Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline in the Global Health Status/QOL Domain at Weeks 12 and 24 | Week 24 | 14.9 percentage of participants |
| Lenalidomide | Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline in the Global Health Status/QOL Domain at Weeks 12 and 24 | Week 24 | 26.5 percentage of participants |
| Lenalidomide | Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline in the Global Health Status/QOL Domain at Weeks 12 and 24 | Week 12 | 22.1 percentage of participants |
Comparison: Week 12p-value: 0.792Fisher Exact
Comparison: Week 24p-value: 0.279Fisher Exact
Secondary
Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline Within the Physical Functioning Domain at Weeks 12 and 24
The European Organization for Research and Treatment of Cancer QOL Questionnaire for Patients with Cancer (EORTC QLQ-C30) was a 30-item oncology-specific questionnaire. The questionnaire was developed to assess the quality of life of cancer patients. It contains 30 questions, 24 of which form 9 multi-item scales representing various aspects of HRQOL: 1 global scale, 5 functional scales (Physical, Role, Emotional, Cognitive and Social), and 3 symptom scales (Fatigue, Pain, and Nausea). The remaining 6 items are intended to be mono-item scales describing relevant cancer-oriented symptoms (dyspnea, insomnia, appetite, constipation, diarrhea, financial difficulties). Subscale scores are transformed to a 0 to 100 scale, with higher scores on functional scales indicating better function and higher score on symptom scales indicating worse symptoms. A change of at least 10 points on the standardized domain scores was required for it to be considered clinically meaningful.
Time frame: Baseline, Week 12, ±3 days and Week 24, ±3 days
Population: Analyses were performed based on the HRQoL evaluable population, defined as all randomized participants who completed the baseline assessment and at least one post-baseline assessment with the EORTC QLQ-C-30. Only those with available data at baseline and each time point are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline Within the Physical Functioning Domain at Weeks 12 and 24 | Week 12 | 26.8 percentage of participants |
| Placebo | Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline Within the Physical Functioning Domain at Weeks 12 and 24 | Week 24 | 12.8 percentage of participants |
| Lenalidomide | Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline Within the Physical Functioning Domain at Weeks 12 and 24 | Week 12 | 16.4 percentage of participants |
| Lenalidomide | Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline Within the Physical Functioning Domain at Weeks 12 and 24 | Week 24 | 24.1 percentage of participants |
Comparison: Week 12p-value: 0.119Fisher Exact
Comparison: Week 24p-value: 0.172Fisher Exact
Secondary
Percentage of Participants With a Clinically Meaningful Improvement in QOL (EORTC QLQ-C-30 Scale) From Baseline in Fatigue Domain at Weeks 12 and 24
The European Organization for Research and Treatment of Cancer QOL Questionnaire for Patients with Cancer (EORTC QLQ-C30) was a 30-item oncology-specific questionnaire. The questionnaire was developed to assess the quality of life of cancer patients. It contains 30 questions, 24 of which form 9 multi-item scales representing various aspects of HRQOL: 1 global scale, 5 functional scales (Physical, Role, Emotional, Cognitive and Social), and 3 symptom scales (Fatigue, Pain, and Nausea). The remaining 6 items are intended to be mono-item scales describing relevant cancer-oriented symptoms (dyspnea, insomnia, appetite, constipation, diarrhea, financial difficulties). Subscale scores are transformed to a 0 to 100 scale, with higher scores on functional scales indicating better function and higher score on symptom scales indicating worse symptoms. Improvement means at least 10 points better compared to baseline
Time frame: Baseline, Week 12, ±3 days and Week 24, ±3 days
Population: Analyses were performed based on the Health Related Quality of Life (HRQoL) evaluable population, defined as all randomized participants who completed the baseline assessment and at least one post-baseline assessment for the intent to treat population. Only those with available data at baseline and each time point are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With a Clinically Meaningful Improvement in QOL (EORTC QLQ-C-30 Scale) From Baseline in Fatigue Domain at Weeks 12 and 24 | Week 12 | 30.4 percentage of participants |
| Placebo | Percentage of Participants With a Clinically Meaningful Improvement in QOL (EORTC QLQ-C-30 Scale) From Baseline in Fatigue Domain at Weeks 12 and 24 | Week 24 | 29.8 percentage of participants |
| Lenalidomide | Percentage of Participants With a Clinically Meaningful Improvement in QOL (EORTC QLQ-C-30 Scale) From Baseline in Fatigue Domain at Weeks 12 and 24 | Week 12 | 39.3 percentage of participants |
| Lenalidomide | Percentage of Participants With a Clinically Meaningful Improvement in QOL (EORTC QLQ-C-30 Scale) From Baseline in Fatigue Domain at Weeks 12 and 24 | Week 24 | 38.6 percentage of participants |
Comparison: Week 12p-value: 0.042Fisher Exact
Comparison: Week 24p-value: 0.448Fisher Exact
Secondary
Time to 56-Day RBC-Transfusion-Independent (TI) Response as Determined by the Sponsor
The time to the first 56-day RBC-transfusion-independent response was calculated for participants who achieved a response. The day from the first dose of study drug to the date at which RBC-transfusion-independence starts was achieved and calculated using: Start date of the first response period - the date of the first study drug +1. A responder was defined as a participant who had a ≥ 56 consecutive days of RBC-transfusion-free period after the first dose of study drug in the treatment phase.
Time frame: From first dose of study drug until 28 days after the last dose of study drug, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.
Population: The analysis was conducted only for those participants who achieved a 56-day TI response according to the sponsor's assessment. Responders in the intent to treat population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to 56-Day RBC-Transfusion-Independent (TI) Response as Determined by the Sponsor | 0.3 weeks |
| Lenalidomide | Time to 56-Day RBC-Transfusion-Independent (TI) Response as Determined by the Sponsor | 10.1 weeks |
Post Hoc
Percentage of Participants Who Achieved an Erythroid Response Based on Original IWG 2006 Criteria
A participant was considered as having achieved an erythroid response when: \- a Hgb increase ≥1.5 g/dL compared to baseline and confirmed by another central laboratory hemoglobin value at 4 to 8 weeks after the first Hgb measurement that had also increased ≥1.5 g/dL for at least 8 weeks. All Hgb values during this time interval must have had a ≥ 1.5 g/dL increase (ie, no central laboratory Hgb increase during this timeframe can be less than a 1.5 g/dL) OR - had an absolute reduction of 4 RBC transfusion units over any consecutive 56 days period compared to the baseline transfusion burden. The baseline transfusion burden is the number of units over the 112 days prior to randomization divided by 2. Only transfusions given for a pre-transfusion Hgb value of 9.5 g/dL or less may be used in this response assessment.
Time frame: From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.
Population: Intent to treat population includes all participants who were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved an Erythroid Response Based on Original IWG 2006 Criteria | 20.3 percentage of participants |
| Lenalidomide | Percentage of Participants Who Achieved an Erythroid Response Based on Original IWG 2006 Criteria | 35.6 percentage of participants |
p-value: 0.01795% CI: [1.083, 2.856]Fisher Exact