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

NCT01029262 | Completed Phase 3 Results DMC

• 1 other identifier: CC-5013-MDS-005
• Study Type: interventional
• Target: 239
• Locations: 15 countries
• Sites: 94

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.

Conditions

Anemia

Keywords

Myelodysplastic Syndromes; MDS; transfusion dependent anemia; Erythropoiesis stimulating agents; non-del 5q

Outcome Measures

Primary Outcomes (2)

• 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

  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.

• 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.

  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 (26)

• 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.

• 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.

• 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.

• 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.

• 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.

Study Arms (2)

Arm #1 - Lenalidomide plus placebo

EXPERIMENTAL

Lenalidomide 10 mg by mouth (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.

Drug: Lenalidomide

Arm #2 - placebo

PLACEBO COMPARATOR

Three placebo capsules once daily for at least 168 days until disease progression occurred, intolerable side effects or withdrawal of consent.

Other: Placebo

Interventions

Lenalidomide DRUG

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)

Also known as: Revlimid, CC-5013

Arm #1 - Lenalidomide plus placebo

Placebo OTHER

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)

Arm #2 - placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Celgene: lead

Study Sites (99)

University of California at Los Angeles

Los Angeles, California, 90095, United States

Location

Southern Illinois Hematology Oncology

Centralia, Illinois, 62801, United States

Location

Dartmouth Hitchcock Medical Center Norris Cotton Cancer Center

Lebanon, New Hampshire, 03756, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Wollongong Hospital

Wollongong, New South Wales, 2500, Australia

Location

Royal Adelaide Hospital Institute of Medical and Veterinary Science

Adelaide, South Australia, 5000 SA, Australia

Location

Princess Alexandra Hospital

Woolloongabba, 4102, Australia

Location

Medizinische Universitat Innsbruck

Innsbruck, 6020, Austria

Location

Krankenhaus der Elisabethinen Linz, I Interne Abteilung

Linz, 4020, Austria

Location

Universitatsklinik fur Innere Medizin Salzburg

Salzburg, 5020, Austria

Location

Wiener Gebietskrankenkasse-Hanusch-Krankenhaus

Vienna, 1140, Austria

Location

Klinikum Wels-Grieskirchen GmbH

Weis, 4600, Austria

Location

AZ St-Jan Brugge Oostende AV

Bruges, 8000, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

Grand Hopital de Charleroi

Charleroi, 6000, Belgium

Location

Universitair Ziekenhuis Antwerpen

Edegem, 2650, Belgium

Location

Centre Hospitalier Universitaire de Liege

Liège, 4000, Belgium

Location

Center Hospitalier Universitaire Ambroise Pare

Mons, 7000, Belgium

Location

Cliniques Universitaires UCL de Mont-Godine

Namur, 5530, Belgium

Location

Tom Baker Cancer Center

Calgary, Alberta, T2N 4N2, Canada

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

Cancer Care Manitoba

Winnepeg, Manitoba, R3E 0V9, Canada

Location

Sunnybrook Regional Cancer Center

Toronto, Ontario, M4N 3M5, Canada

Location

Princess Margaret Hospital and University of Toronto

Toronto, Ontario, M5G 2M9, Canada

Location

Maisonneuve Rosemont

Montreal, Quebec, H1T 2M4, Canada

Location

McGill University, Dept. Oncology Clinical Research Program

Montreal, Quebec, H2W 1S6, Canada

Location

Hopital du Sacre-Coeur de Montreal

Montreal, Quebec, H4J 1C5, Canada

Location

Fakultni nemocnice Brno

Brno, 625 00, Czechia

Location

Fakultni nemocnice Olomouc

Olomouc, 77520, Czechia

Location

Ustav hematologie a krevni transfuze

Prague, 128 20, Czechia

Location

Vseobecna Fakultni Nemocnice v Praze

Prague, 12808, Czechia

Location

CHU d'Angers

Angers, 49033, France

Location

Hopital Avicenne

Bobigny, 93009, France

Location

Hopital A. Michallon

La Tronche, 38700, France

Location

CHRU de Lille-Hopital Claude Huriez Service des Maladies du Sang

Lille, 59037, France

Location

Institut Paoli-Calmettes

Marseille, 13273, France

Location

Groupe hospitalier Cochin Saint-Vincent de Paul

Paris, 75679, France

Location

Universitat zu Koln

Cologne, 50924, Germany

Location

BAG Freiberg-Richter, Jacobash, Illmer, Wolf

Dresden, 1307, Germany

Location

Sankt Johannes Hospital Duisburg

Duisberg, 47166, Germany

Location

Universitätsklinikum Düsseldorf

Düesseldorf, 40211, Germany

Location

Marien Hospital

Düsseldorf, 40479, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Klinikum Mannheim der Universitat Heidelberg

Heidelberg, 69120, Germany

Location

Universitatsklinikum Mannheim

Mannheim, 68135, Germany

Location

TU München - Klinikum rechts der Isar

München, 81675, Germany

Location

Rabin Medical Center

Petah Tikva, 49100, Israel

Location

Tel-Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

The Chaim Sheba Medical Center

Tel Litwinsky, 52621, Israel

Location

Az. Osp. SS.Antonio e Biagio - SC Ematologia

Alessandria, 15100, Italy

Location

A.O.U. di Bologna Policlinico S.Orsola-Malpighi

Bologna, 40138, Italy

Location

P.O. Ospedale Roberto Binaghi (UNI CA/ASL 8)

Cagliari, 09100, Italy

Location

Azienda Ospedaliero-Universitaria di Cagliari

Cagliari, 09121, Italy

Location

Azienda Ospedaliero-Universitaria Careggi

Florence, 50139, Italy

Location

Azienda Ospedaliera Cardarelli

Naples, 80131, Italy

Location

AOU San Luigi Gonzaga

Orbassano, 10043, Italy

Location

IRCCS Centro di Riferimento Oncologico di Basilicata di Rionero in Vulture

Rionero in Vulture, Italy

Location

Azienda Ospedaliera Universitaria Policlinico Tor Vergata

Roma, 00133, Italy

Location

Azienda Policlinico Umberto I, Universita La Sapienzadi Roma

Roma, 00161, Italy

Location

Policlinico Agostino Gemelli - Istituto di Ematologia

Roma, 00168, Italy

Location

Policlinico Univeristario di Udine

Udine, 33100, Italy

Location

Hiroshima University Hospital

Hiroshima, Japan

Location

Tokai University School of Medicine

Isehara City, Kanagawa, 259-1193, Japan

Location

Kameda General Hospital

Kamogawa, 296-8602, Japan

Location

Kanazawa University Hospital

Kanazawa, Japan

Location

Nagasaki Unversity Hospital

Nagasaki, Japan

Location

National Hospital Organization Nagoya Medical Center

Nagoya, 460-0001, Japan

Location

Osaka Red Cross Hospital

Osaka, Japan

Location

Tohoku University Hospital

Sendai, 980-8574, Japan

Location

Japanese Red Cross Medical Center

Shibuya City, 150-8935, Japan

Location

Jichi Medical University Hospital

Shimotsuke, Japan

Location

Kanto Medical Center NTT EC

Shinagawa City, Japan

Location

Katedra i Klinika Hematologii i Transplantacji Szpiku - SLASKIEGO UNIWERSYTETU MEDYCZNEGO

Gdansk, 80-119, Poland

Location

Uniwersytet Medyczny w Lodzi

Lodz, 93-510, Poland

Location

Instytut Hematologii i Transfuzjologii, Klinika Hematologii

Warsaw, 02-776, Poland

Location

Hospitais da Universidade de Coimbra

Coimbra, 3000-075, Portugal

Location

Instituto Portugues de Oncologia de Lisboa

Lisbon, 1090-023, Portugal

Location

Hospital Geral de Santo Antonio

Porto, 4099-001, Portugal

Location

Hospital Clinic Provincial de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

Hospital Son Llatzer

Palma de Mallorca, 7198, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario Virgen Del Rocio

Seville, 41013, Spain

Location

Hospital Universitario La Fe

Valencia, 46009, Spain

Location

Gazi Universitesi Tip Fakltesi

Ankara, 06500, Turkey (Türkiye)

Location

Akdeniz Universitesi Tip Fakultesi

Antalya, 07503, Turkey (Türkiye)

Location

Istanbul Universitesi Istanbul

Istanbul, 34390, Turkey (Türkiye)

Location

Dokuz Eylul Universitesi Tip Faiultesi

Izimir, 35340, Turkey (Türkiye)

Location

Royal Bournemouth Hospital

Bournemouth, BH7 7DW, United Kingdom

Location

University Hospital of Wales

Cardiff, CF14 4XN, United Kingdom

Location

Saint James University Hospital

Leeds, LS9 7TF, United Kingdom

Location

Barts Cancer Institute, Queen Mary University of London, Charterhouse Square

London, EC1A 7BE, United Kingdom

Location

King's College Hospital

London, SE5 9RS, United Kingdom

Location

Christie Hospital

Manchester, M20 4BX, United Kingdom

Location

John Radcliffe Hospital

Oxford, OX3 9DU, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 27354480 RESULT

• 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.

  PMID: 32064987 DERIVED

• 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.

  PMID: 29322849 DERIVED

MeSH Terms

Conditions

Anemia; Myelodysplastic Syndromes

Interventions

Lenalidomide

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Anne McClain, Senior Study Manager
• Organization: Celgene Corporation

clinicaltrialdisclosure@celgene.com

888-260-1588

Study Officials

• Albert Hoenekopp, MD

  Celgene Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2009
• First Posted: December 9, 2009
• Study Start: January 26, 2010
• Primary Completion: March 17, 2013
• Study Completion: May 9, 2018
• Last Updated: June 25, 2019
• Results First Posted: June 18, 2015

Record last verified: 2019-06

Locations

BE (7); ES (7); AU (3); IL (3); JP (11); PL (3); IT (12); DE (9); FR (6); US (7); TU (4); GB (7); CZ (4); CA (8); PT (3)