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NCT01029262: MDS-005

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

Completed Phase 3 Results posted Last updated 25 June 2019
What this trial tests

Phase 3 trial testing Lenalidomide in Anemia in 239 participants. Completed in 9 May 2018.

Timeline
26 January 2010
Primary endpoint
17 March 2013
9 May 2018

Quick facts

Lead sponsorCelgene
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment239
Start date26 January 2010
Primary completion17 March 2013
Estimated completion9 May 2018
Sites99 locations across France, Italy, Japan, Belgium, Austria, United Kingdom, Germany, Israel

Drugs / interventions tested

Conditions studied

Sponsor

Celgene — full company profile →

Who can join

18 and older, any sex, with Anemia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence for ≥ 56 Days as Determined by an Independent Review Committee (IRC) Primary · 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

GroupValue95% CI
Placebo2.5
Lenalidomide26.9
Percentage of Participants With a Erythroid Gene Signature Who Achieved RBC Transfusion Independence for ≥ 56 Days as Determined by an Independent Review Committee (IRC) Primary · 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.

GroupValue95% CI
Placebo0.0
Lenalidomide7.1
Percentage of Participants Who Achieved RBC Transfusion Independence With a Duration of ≥ 24 Weeks (168 Days) as Determined by the Sponsor Secondary · 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.

GroupValue95% CI
Placebo0.0
Lenalidomide17.5
Kaplan Meier Estimates of Duration of 56-day RBC Transfusion Independence Response as Determined by the Sponsor Secondary · 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. * Fo

GroupValue95% CI
PlaceboNANA – NA
Lenalidomide30.920.7 – 59.1
Percentage of Participants Who Achieved an Erythroid Response Based on the Modified International Working Group (IWG) 2006 Criteria Secondary · 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 tr

GroupValue95% CI
Placebo30.4
Lenalidomide38.8
Time to 56-Day RBC-Transfusion-Independent (TI) Response as Determined by the Sponsor Secondary · 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.

GroupValue95% CI
Placebo0.30.3 – 0.3
Lenalidomide10.10.3 – 23.6
Kaplan Meier Estimates for Progression to Acute Myeloid Leukemia (AML) Secondary · 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.

GroupValue95% CI
PlaceboNANA – NA
LenalidomideNA5.2 – NA
Kaplan Meier Estimate for Overall Survival (OS) Secondary · 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.

GroupValue95% CI
Placebo3.02.3 – NA
Lenalidomide3.82.9 – 4.8
Number of Participants With Treatment Emergent Adverse Events (TEAE) Secondary · 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

At least 1 TEAE
GroupValue95% CI
Placebo74
Lenalidomide160
≥ 1 Treatment Related AE (TEAE)
GroupValue95% CI
Placebo42
Lenalidomide144
≥ 1 Treatment related TEAE Causing Discontinuation
GroupValue95% CI
Placebo3
Lenalidomide40
≥ 1 TEAE Leading to Dose Reduction
GroupValue95% CI
Placebo1
Lenalidomide10
≥ 1 TEAE Leading to Dose Interruption
GroupValue95% CI
Placebo11
Lenalidomide89
≥ 1 TEAE Leading to Dose Interruption & Reduction
GroupValue95% CI
Placebo5
Lenalidomide68
≥ 1 TEAE Leading to Discontinuation of Study Drug
GroupValue95% CI
Placebo9
Lenalidomide51
≥ 1 Serious TEAE
GroupValue95% CI
Placebo16
Lenalidomide62
Compliance Rates Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) From Baseline to Week 48 Secondary · 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 (dyspne

Baseline
GroupValue95% CI
Placebo88.6
Lenalidomide90
Week 12
GroupValue95% CI
Placebo78.5
Lenalidomide83.8
Week 24
GroupValue95% CI
Placebo80.6
Lenalidomide85.8
Week 36
GroupValue95% CI
Placebo100
Lenalidomide80.5
Week 48
GroupValue95% CI
Placebo50
Lenalidomide71.9
Mean Change From Baseline in the EORTC QLQ-C30 Fatigue Domain at Week 12 and 24 Secondary · 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 o

Week 12
GroupValue95% CI
Placebo0.6± 17.53
Lenalidomide2.4± 28.26
Week 24
GroupValue95% CI
Placebo7.6± 20.74
Lenalidomide-1.5± 26.42
Mean Change From Baseline in the EORTC QLQ-C30 Dyspnea Domain at Week 12 and 24 Secondary · 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 o

Week 12
GroupValue95% CI
Placebo0.6± 28.06
Lenalidomide2.2± 29.92
Week 24
GroupValue95% CI
Placebo4.3± 26.57
Lenalidomide1.2± 26.26

Adverse events — posted to ClinicalTrials.gov

Time frame: From the first dose of study drug through 28 days after last dose; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide treatment group and 529 days in the placebo group. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 16/79 (20%)
Deaths: 43/79
Lenalidomide
Serious: 62/160 (39%)
Deaths: 94/160

Serious adverse events (91 terms)

ReactionSystemPlaceboLenalidomide
PNEUMONIAInfections and infestations
ANAEMIABlood and lymphatic system disorders
NEUTROPENIABlood and lymphatic system disorders
CARDIAC FAILURECardiac disorders
NEUTROPENIC SEPSISInfections and infestations
PLEURAL EFFUSIONRespiratory, thoracic and mediastinal disorders
DEEP VEIN THROMBOSISVascular disorders
ATRIAL FIBRILLATIONCardiac disorders
MYOCARDIAL INFARCTIONCardiac disorders
GENERAL PHYSICAL HEALTH DETERIORATIONGeneral disorders
BRONCHITISInfections and infestations
CELLULITISInfections and infestations
URINARY TRACT INFECTIONInfections and infestations
FEMUR FRACTUREInjury, poisoning and procedural complications
TRAUMATIC INTRACRANIAL HAEMORRHAGEInjury, poisoning and procedural complications
ACUTE MYELOID LEUKAEMIANeoplasms benign, malignant and unspecified (incl cysts and polyps)
MYELODYSPLASTIC SYNDROMENeoplasms benign, malignant and unspecified (incl cysts and polyps)
TRANSIENT ISCHAEMIC ATTACKNervous system disorders
MENTAL STATUS CHANGESPsychiatric disorders
SKIN ULCERSkin and subcutaneous tissue disorders
HAEMOLYSISBlood and lymphatic system disorders
PANCYTOPENIABlood and lymphatic system disorders
THROMBOCYTOPENIABlood and lymphatic system disorders
ACUTE MYOCARDIAL INFARCTIONCardiac disorders
ATRIAL FLUTTERCardiac disorders
Other adverse events (43 terms — click to expand)

ReactionSystemPlaceboLenalidomide
NEUTROPENIABlood and lymphatic system disorders
DIARRHOEAGastrointestinal disorders
THROMBOCYTOPENIABlood and lymphatic system disorders
ASTHENIAGeneral disorders
CONSTIPATIONGastrointestinal disorders
FATIGUEGeneral disorders
OEDEMA PERIPHERALGeneral disorders
RASHSkin and subcutaneous tissue disorders
PRURITUSSkin and subcutaneous tissue disorders
LEUKOPENIABlood and lymphatic system disorders
PYREXIAGeneral disorders
NAUSEAGastrointestinal disorders
NASOPHARYNGITISInfections and infestations
DECREASED APPETITEMetabolism and nutrition disorders
MUSCLE SPASMSMusculoskeletal and connective tissue disorders
PAIN IN EXTREMITYMusculoskeletal and connective tissue disorders
WEIGHT DECREASEDInvestigations
COUGHRespiratory, thoracic and mediastinal disorders
BACK PAINMusculoskeletal and connective tissue disorders
OVERDOSEInjury, poisoning and procedural complications
DYSPNOEARespiratory, thoracic and mediastinal disorders
ARTHRALGIAMusculoskeletal and connective tissue disorders
VOMITINGGastrointestinal disorders
ALANINE AMINOTRANSFERASE INCREASEDInvestigations
DIZZINESSNervous system disorders
ABDOMINAL PAIN UPPERGastrointestinal disorders
DRY SKINSkin and subcutaneous tissue disorders
ABDOMINAL PAINGastrointestinal disorders
INFLUENZAInfections and infestations
HYPOKALAEMIAMetabolism and nutrition disorders
EPISTAXISRespiratory, thoracic and mediastinal disorders
URINARY TRACT INFECTIONInfections and infestations
HEADACHENervous system disorders
INSOMNIAPsychiatric disorders
ANAEMIABlood and lymphatic system disorders
CONJUNCTIVITISEye disorders
DYSPEPSIAGastrointestinal disorders
MYALGIAMusculoskeletal and connective tissue disorders
NIGHT SWEATSSkin and subcutaneous tissue disorders
UPPER RESPIRATORY TRACT INFECTIONInfections and infestations

Most-reported serious reactions: PNEUMONIA, ANAEMIA, NEUTROPENIA, CARDIAC FAILURE, NEUTROPENIC SEPSIS, PLEURAL EFFUSION, DEEP VEIN THROMBOSIS, ATRIAL FIBRILLATION.

Data from ClinicalTrials.gov NCT01029262 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Molecular Targeted Therapy in Myelodysplastic Syndromes: New Options for Tailored Treatments.
    Pagliuca S, Gurnari C, Visconte V. · · 2021 · cited 9× · PMID 33668555 · DOI 10.3390/cancers13040784
  2. Impact of somatic mutations on response to lenalidomide in lower-risk non-del(5q) myelodysplastic syndromes patients.
    Santini V, Fenaux P, Giagounidis A, Platzbecker U, et al · · 2021 · cited 7× · PMID 32661294 · DOI 10.1038/s41375-020-0961-3
  3. Next-generation therapy for lower-risk MDS.
    Sébert M. · · 2023 · cited 5× · PMID 38066862 · DOI 10.1182/hematology.2023000520
  4. Safety profile of lenalidomide in patients with lower-risk myelodysplastic syndromes without del(5q): results of a phase 3 trial.
    Almeida A, Fenaux P, Garcia-Manero G, Goldberg SL, et al · · 2018 · cited 5× · PMID 29322849 · DOI 10.1080/10428194.2017.1421758
  5. Achievement of red blood cell transfusion independence in red blood cell transfusion-dependent patients with lower-risk non-del(5q) myelodysplastic syndromes correlates with serum erythropoietin levels.
    Santini V, Almeida A, Giagounidis A, Skikne B, et al · · 2020 · cited 4× · PMID 32064987 · DOI 10.1080/10428194.2020.1719088
  6. Identification of Lenalidomide Sensitivity and Resistance Mechanisms in Non-Del(5q) Myelodysplastic Syndromes.
    Drusbosky LM, Cogle CR. · · 2020 · cited 2× · PMID 32397113 · DOI 10.3390/ijms21093323
  7. A Review of Patient-Reported Outcomes and Clinical Outcomes in Acute and Chronic Myeloid and Lymphoid Leukemias.
    Chan B, Balar E, Villalona S, Karp J, et al · · 2026 · PMID 41718417 · DOI 10.3390/hematolrep18010015
  8. Updates in low/intermediate-risk MDS.
    Carraway HE. · · 2025 · PMID 41348013 · DOI 10.1182/hematology.2025000768

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