Clinical trial NCT01029262: A Study of Lenalidomide Versus Placebo in Subjects With Transfusion Dependent Anemia in Lower Risk Myelodysplastic Syndrome (MDS) Without Del 5q
Official title: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study To Compare The Efficacy And Safety of Lenalidomide (Revlimid®) Versus Placebo In Subjects With Transufsion-Dependent Anemia Due to IPSS Low Or Imtermidate-1 Risk Myelodysplastic Syndromes Without Deletion 5Q(31) And Unresponsive Or Refractory To Erthropoiesis-Stimulating Agents
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Anemia
Keywords: Myelodysplastic Syndromes
MDS
transfusion dependent anemia
Erythropoiesis stimulating agents
non-del 5q
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2009-12-09
Enrollment: 239
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence for ≥ 56 Days as Determined by an Independent Review Committee (IRC)
timeFrame: 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.
measure: Percentage of Participants With a Erythroid Gene Signature Who Achieved RBC Transfusion Independence for ≥ 56 Days as Determined by an Independent Review Committee (IRC)
timeFrame: 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.
Secondary outcomes:
measure: Percentage of Participants Who Achieved RBC Transfusion Independence With a Duration of ≥ 24 Weeks (168 Days) as Determined by the Sponsor
timeFrame: 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.
measure: Kaplan Meier Estimates of Duration of 56-day RBC Transfusion Independence Response as Determined by the Sponsor
timeFrame: Response was assessed up to the end of treatment; up to the data cut-off date of 17 Mar 2014.
measure: Percentage of Participants Who Achieved an Erythroid Response Based on the Modified International Working Group (IWG) 2006 Criteria
timeFrame: 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.
measure: Time to 56-Day RBC-Transfusion-Independent (TI) Response as Determined by the Sponsor
timeFrame: 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.
measure: Kaplan Meier Estimates for Progression to Acute Myeloid Leukemia (AML)
timeFrame: 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.
measure: Kaplan Meier Estimate for Overall Survival (OS)
timeFrame: From randomization to final data cut-off date of 03 July 2018; maximum survival follow up was 6.4 years
measure: Number of Participants With Treatment Emergent Adverse Events (TEAE)
timeFrame: 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.
measure: Compliance Rates Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) From Baseline to Week 48
timeFrame: 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
measure: Mean Change From Baseline in the EORTC QLQ-C30 Fatigue Domain at Week 12 and 24
timeFrame: Baseline and Week 12, ±3 days and Week 24, ±3 days
measure: Mean Change From Baseline in the EORTC QLQ-C30 Dyspnea Domain at Week 12 and 24
timeFrame: Baseline and Week 12, ±3 days and Week 24, ±3 days
measure: Mean Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain at Week 12 and 24
timeFrame: Baseline and Week 12, ±3 days and Week 24, ±3 days
measure: Mean Change From Baseline in the EORTC QLQ-C30 Global Health Status/Quality of Life (QOL) Domain at Week 12 and 24
timeFrame: Baseline and Week 12, ±3 days and Week 24, ±3 days
measure: Mean Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain at Week 12 and 24
timeFrame: Baseline and Week 12, ±3 days and Week 24, ±3 days
measure: Mean Change From Baseline in Fatigue Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24
timeFrame: Baseline, Week 12, ±3 days and Week 24, ±3 days
measure: Mean Change From Baseline in the Dyspnea Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24
timeFrame: Baseline, Week 12, ±3 days and Week 24, ±3 days
measure: Mean Change From Baseline in the Physical Functioning Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24
timeFrame: Baseline, Week 12, ±3 days and Week 24, ±3 days
measure: 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
timeFrame: Baseline, Week 12, ±3 days and Week 24, ±3 days
measure: Mean Change From Baseline in the Emotional Functioning Domain Associated With the EORTC QLQ-C30 Scale at Weeks 12 and 24
timeFrame: Baseline, Week 12, ±3 days and Week 24, ±3 days
measure: 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
timeFrame: Baseline, Week 12, ±3 days and Week 24, ±3 days
measure: 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
timeFrame: Baseline, Week 12, ±3 days and Week 24, ±3 days
measure: 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
timeFrame: Baseline, Week 12, ±3 days and Week 24, ±3 days
measure: 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
timeFrame: Baseline, Week 12, ±3 days and Week 24, ±3 days
measure: 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
timeFrame: Baseline, Week 12, ±3 days and Week 24, ±3 days
measure: Healthcare Resource Utilization (HRU): Rate of Inpatient Hospitalizations Related to Adverse Events Per Person Year
timeFrame: 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.
measure: Healthcare Resource Utilization (HRU): Duration of Hospitalizations Due to Adverse Events
timeFrame: 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.
measure: Healthcare Resource Utilization (HRU): Number of Days of Hospitalization Due to Adverse Events Per Person-Years
timeFrame: 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.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California at Los Angeles
state: California
city: Centralia
country: United States
facility: Southern Illinois Hematology Oncology
state: Illinois
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center Norris Cotton Cancer Center
state: New Hampshire
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Wollongong
country: Australia
facility: Wollongong Hospital
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital Institute of Medical and Veterinary Science
state: South Australia
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
city: Innsbruck
country: Austria
facility: Medizinische Universitat Innsbruck
city: Linz
country: Austria
facility: Krankenhaus der Elisabethinen Linz, I Interne Abteilung
city: Salzburg
country: Austria
facility: Universitatsklinik fur Innere Medizin Salzburg
city: Weis
country: Austria
facility: Klinikum Wels-Grieskirchen GmbH
city: Wien
country: Austria
facility: Wiener Gebietskrankenkasse-Hanusch-Krankenhaus
city: Brugge
country: Belgium
facility: AZ St-Jan Brugge Oostende AV
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Charleroi
country: Belgium
facility: Grand Hopital de Charleroi
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Liege
country: Belgium
facility: Centre Hospitalier Universitaire de Liege
city: Mons
country: Belgium
facility: Center Hospitalier Universitaire Ambroise Pare
city: Namur
country: Belgium
facility: Cliniques Universitaires UCL de Mont-Godine
city: Calgary
country: Canada
facility: Tom Baker Cancer Center
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Winnepeg
country: Canada
facility: Cancer Care Manitoba
state: Manitoba
city: Toronto
country: Canada
facility: Sunnybrook Regional Cancer Center
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital and University of Toronto
state: Ontario
city: Montreal
country: Canada
facility: Maisonneuve Rosemont
state: Quebec
city: Montreal
country: Canada
facility: McGill University, Dept. Oncology Clinical Research Program
state: Quebec
city: Montreal
country: Canada
facility: Hopital du Sacre-Coeur de Montreal
state: Quebec
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc
city: Prague
country: Czechia
facility: Vseobecna Fakultni Nemocnice v Praze
city: Praha
country: Czechia
facility: Ustav hematologie a krevni transfuze
city: Angers
country: France
facility: CHU d'Angers
city: Bobigny Cedex
country: France
facility: Hopital Avicenne
city: La Tronche
country: France
facility: Hopital A. Michallon
city: Lille
country: France
facility: CHRU de Lille-Hopital Claude Huriez Service des Maladies du Sang
city: Marseille cedex
country: France
facility: Institut Paoli-Calmettes
city: Paris Cedex
country: France
facility: Groupe hospitalier Cochin Saint-Vincent de Paul
city: Dresden
country: Germany
facility: BAG Freiberg-Richter, Jacobash, Illmer, Wolf
city: Duesseldorf
country: Germany
facility: Marien Hospital
city: Duisberg
country: Germany
facility: Sankt Johannes Hospital Duisburg
city: Düesseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: Klinikum Mannheim der Universitat Heidelberg
city: Köln
country: Germany
facility: Universitat zu Koln
city: Mannheim
country: Germany
facility: Universitatsklinikum Mannheim
city: München
country: Germany
facility: TU München - Klinikum rechts der Isar
city: Petach-Tikva
country: Israel
facility: Rabin Medical Center
city: Tel Hashomer
country: Israel
facility: The Chaim Sheba Medical Center
city: Tel-Aviv
country: Israel
facility: Tel-Aviv Sourasky Medical Center
city: Alessandria
country: Italy
facility: Az. Osp. SS.Antonio e Biagio - SC Ematologia
city: Bologna
country: Italy
facility: A.O.U. di Bologna Policlinico S.Orsola-Malpighi
city: Cagliari
country: Italy
facility: P.O. Ospedale Roberto Binaghi (UNI CA/ASL 8)
city: Cagliari
country: Italy
facility: Azienda Ospedaliero-Universitaria di Cagliari
city: Firenze
country: Italy
facility: Azienda Ospedaliero-Universitaria Careggi
city: Naples
country: Italy
facility: Azienda Ospedaliera Cardarelli
city: Orbassano
country: Italy
facility: AOU San Luigi Gonzaga
city: Rionero in Vulture
country: Italy
facility: IRCCS Centro di Riferimento Oncologico di Basilicata di Rionero in Vulture
city: Roma
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Tor Vergata
city: Roma
country: Italy
facility: Azienda Policlinico Umberto I, Universita La Sapienzadi Roma
city: Roma
country: Italy
facility: Policlinico Agostino Gemelli - Istituto di Ematologia
city: Udine
country: Italy
facility: Policlinico Univeristario di Udine
city: Hiroshima
country: Japan
facility: Hiroshima University Hospital
city: Isehara City, Kanagawa
country: Japan
facility: Tokai University School of Medicine
city: Kamogawa
country: Japan
facility: Kameda General Hospital
city: Kanazawa
country: Japan
facility: Kanazawa University Hospital
city: Nagasaki
country: Japan
facility: Nagasaki Unversity Hospital
city: Nagoya
country: Japan
facility: National Hospital Organization Nagoya Medical Center
city: Osaka
country: Japan
facility: Osaka Red Cross Hospital
city: Sendai
country: Japan
facility: Tohoku University Hospital
city: Shibuya
country: Japan
facility: Japanese Red Cross Medical Center
city: Shimotsuke
country: Japan
facility: Jichi Medical University Hospital
city: Shinagawa
country: Japan
facility: Kanto Medical Center NTT EC
city: Gdansk
country: Poland
facility: Katedra i Klinika Hematologii i Transplantacji Szpiku - SLASKIEGO UNIWERSYTETU MEDYCZNEGO
city: Lodz
country: Poland
facility: Uniwersytet Medyczny w Lodzi
city: Warsaw
country: Poland
facility: Instytut Hematologii i Transfuzjologii, Klinika Hematologii
city: Coimbra
country: Portugal
facility: Hospitais da Universidade de Coimbra
city: Lisboa
country: Portugal
facility: Instituto Portugues de Oncologia de Lisboa
city: Porto
country: Portugal
facility: Hospital Geral de Santo Antonio
city: Barcelona
country: Spain
facility: Hospital Clinic Provincial de Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Malaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Palma de Mallorca
country: Spain
facility: Hospital Son Llatzer
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocio
city: Valencia
country: Spain
facility: Hospital Universitario La Fe
city: Ankara
country: Turkey
facility: Gazi Universitesi Tip Fakltesi
city: Antalya
country: Turkey
facility: Akdeniz Universitesi Tip Fakultesi
city: Istanbul
country: Turkey
facility: Istanbul Universitesi Istanbul
city: Izimir
country: Turkey
facility: Dokuz Eylul Universitesi Tip Faiultesi
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
city: Leeds
country: United Kingdom
facility: Saint James University Hospital
city: London
country: United Kingdom
facility: Barts Cancer Institute, Queen Mary University of London, Charterhouse Square
city: London
country: United Kingdom
facility: King's College Hospital
city: Manchester
country: United Kingdom
facility: Christie Hospital
city: Oxford
country: United Kingdom
facility: John Radcliffe Hospital
Study officials:
affiliation: Celgene Corporation
name: Albert Hoenekopp, MD
role: STUDY_DIRECTOR
References:
citation: Santini V, Almeida A, Giagounidis A, Gropper S, Jonasova A, Vey N, Mufti GJ, Buckstein R, Mittelman M, Platzbecker U, Shpilberg O, Ram R, Del Canizo C, Gattermann N, Ozawa K, Risueno A, MacBeth KJ, Zhong J, Seguy F, Hoenekopp A, Beach CL, Fenaux P. Randomized Phase III Study of Lenalidomide Versus Placebo in RBC Transfusion-Dependent Patients With Lower-Risk Non-del(5q) Myelodysplastic Syndromes and Ineligible for or Refractory to Erythropoiesis-Stimulating Agents. J Clin Oncol. 2016 Sep 1;34(25):2988-96. doi: 10.1200/JCO.2015.66.0118. Epub 2016 Jun 27.
citation: Santini V, Almeida A, Giagounidis A, Skikne B, Beach CL, Weaver J, Tu N, Fenaux P. 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. Leuk Lymphoma. 2020 Jun;61(6):1475-1483. doi: 10.1080/10428194.2020.1719088. Epub 2020 Feb 17.
citation: Almeida A, Fenaux P, Garcia-Manero G, Goldberg SL, Gropper S, Jonasova A, Vey N, Castaneda C, Zhong J, Beach CL, Santini V. Safety profile of lenalidomide in patients with lower-risk myelodysplastic syndromes without del(5q): results of a phase 3 trial. Leuk Lymphoma. 2018 Sep;59(9):2135-2143. doi: 10.1080/10428194.2017.1421758. Epub 2018 Jan 11.