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

NCT ID: NCT01029262

Last Updated: 2019-06-25

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

239 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-01-26

Study Completion Date

2018-05-09

Brief Summary

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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.

Detailed Description

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Conditions

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Anemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Arm #1 - Lenalidomide plus placebo

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.

Group Type EXPERIMENTAL

Lenalidomide

Intervention Type 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)

Arm #2 - placebo

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type 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)

Interventions

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Lenalidomide

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)

Intervention Type DRUG

Placebo

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)

Intervention Type OTHER

Other Intervention Names

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Revlimid CC-5013

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Celgene

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Albert Hoenekopp, MD

Role: STUDY_DIRECTOR

Celgene Corporation

Locations

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University of California at Los Angeles

Los Angeles, California, United States

Site Status

Southern Illinois Hematology Oncology

Centralia, Illinois, United States

Site Status

Dartmouth Hitchcock Medical Center Norris Cotton Cancer Center

Lebanon, New Hampshire, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Wollongong Hospital

Wollongong, New South Wales, Australia

Site Status

Royal Adelaide Hospital Institute of Medical and Veterinary Science

Adelaide, South Australia, Australia

Site Status

Princess Alexandra Hospital

Woolloongabba, , Australia

Site Status

Medizinische Universitat Innsbruck

Innsbruck, , Austria

Site Status

Krankenhaus der Elisabethinen Linz, I Interne Abteilung

Linz, , Austria

Site Status

Universitatsklinik fur Innere Medizin Salzburg

Salzburg, , Austria

Site Status

Wiener Gebietskrankenkasse-Hanusch-Krankenhaus

Vienna, , Austria

Site Status

Klinikum Wels-Grieskirchen GmbH

Weis, , Austria

Site Status

AZ St-Jan Brugge Oostende AV

Bruges, , Belgium

Site Status

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Site Status

Grand Hopital de Charleroi

Charleroi, , Belgium

Site Status

Universitair Ziekenhuis Antwerpen

Edegem, , Belgium

Site Status

Centre Hospitalier Universitaire de Liege

Liège, , Belgium

Site Status

Center Hospitalier Universitaire Ambroise Pare

Mons, , Belgium

Site Status

Cliniques Universitaires UCL de Mont-Godine

Namur, , Belgium

Site Status

Tom Baker Cancer Center

Calgary, Alberta, Canada

Site Status

University of Alberta Hospital

Edmonton, Alberta, Canada

Site Status

Cancer Care Manitoba

Winnepeg, Manitoba, Canada

Site Status

Sunnybrook Regional Cancer Center

Toronto, Ontario, Canada

Site Status

Princess Margaret Hospital and University of Toronto

Toronto, Ontario, Canada

Site Status

Maisonneuve Rosemont

Montreal, Quebec, Canada

Site Status

McGill University, Dept. Oncology Clinical Research Program

Montreal, Quebec, Canada

Site Status

Hopital du Sacre-Coeur de Montreal

Montreal, Quebec, Canada

Site Status

Fakultni nemocnice Brno

Brno, , Czechia

Site Status

Fakultni nemocnice Olomouc

Olomouc, , Czechia

Site Status

Ustav hematologie a krevni transfuze

Prague, , Czechia

Site Status

Vseobecna Fakultni Nemocnice v Praze

Prague, , Czechia

Site Status

CHU d'Angers

Angers, , France

Site Status

Hopital Avicenne

Bobigny, , France

Site Status

Hopital A. Michallon

La Tronche, , France

Site Status

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

Lille, , France

Site Status

Institut Paoli-Calmettes

Marseille, , France

Site Status

Groupe hospitalier Cochin Saint-Vincent de Paul

Paris, , France

Site Status

Universitat zu Koln

Cologne, , Germany

Site Status

BAG Freiberg-Richter, Jacobash, Illmer, Wolf

Dresden, , Germany

Site Status

Sankt Johannes Hospital Duisburg

Duisberg, , Germany

Site Status

Universitätsklinikum Düsseldorf

Düesseldorf, , Germany

Site Status

Marien Hospital

Düsseldorf, , Germany

Site Status

Medizinische Hochschule Hannover

Hanover, , Germany

Site Status

Klinikum Mannheim der Universitat Heidelberg

Heidelberg, , Germany

Site Status

Universitatsklinikum Mannheim

Mannheim, , Germany

Site Status

TU München - Klinikum rechts der Isar

München, , Germany

Site Status

Rabin Medical Center

Petah Tikva, , Israel

Site Status

Tel-Aviv Sourasky Medical Center

Tel Aviv, , Israel

Site Status

The Chaim Sheba Medical Center

Tel Litwinsky, , Israel

Site Status

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

Alessandria, , Italy

Site Status

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

Bologna, , Italy

Site Status

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

Cagliari, , Italy

Site Status

Azienda Ospedaliero-Universitaria di Cagliari

Cagliari, , Italy

Site Status

Azienda Ospedaliero-Universitaria Careggi

Florence, , Italy

Site Status

Azienda Ospedaliera Cardarelli

Naples, , Italy

Site Status

AOU San Luigi Gonzaga

Orbassano, , Italy

Site Status

IRCCS Centro di Riferimento Oncologico di Basilicata di Rionero in Vulture

Rionero in Vulture, , Italy

Site Status

Azienda Ospedaliera Universitaria Policlinico Tor Vergata

Roma, , Italy

Site Status

Azienda Policlinico Umberto I, Universita La Sapienzadi Roma

Roma, , Italy

Site Status

Policlinico Agostino Gemelli - Istituto di Ematologia

Roma, , Italy

Site Status

Policlinico Univeristario di Udine

Udine, , Italy

Site Status

Hiroshima University Hospital

Hiroshima, , Japan

Site Status

Tokai University School of Medicine

Isehara City, Kanagawa, , Japan

Site Status

Kameda General Hospital

Kamogawa, , Japan

Site Status

Kanazawa University Hospital

Kanazawa, , Japan

Site Status

Nagasaki Unversity Hospital

Nagasaki, , Japan

Site Status

National Hospital Organization Nagoya Medical Center

Nagoya, , Japan

Site Status

Osaka Red Cross Hospital

Osaka, , Japan

Site Status

Tohoku University Hospital

Sendai, , Japan

Site Status

Japanese Red Cross Medical Center

Shibuya City, , Japan

Site Status

Jichi Medical University Hospital

Shimotsuke, , Japan

Site Status

Kanto Medical Center NTT EC

Shinagawa City, , Japan

Site Status

Katedra i Klinika Hematologii i Transplantacji Szpiku - SLASKIEGO UNIWERSYTETU MEDYCZNEGO

Gdansk, , Poland

Site Status

Uniwersytet Medyczny w Lodzi

Lodz, , Poland

Site Status

Instytut Hematologii i Transfuzjologii, Klinika Hematologii

Warsaw, , Poland

Site Status

Hospitais da Universidade de Coimbra

Coimbra, , Portugal

Site Status

Instituto Portugues de Oncologia de Lisboa

Lisbon, , Portugal

Site Status

Hospital Geral de Santo Antonio

Porto, , Portugal

Site Status

Hospital Clinic Provincial de Barcelona

Barcelona, , Spain

Site Status

Hospital Universitario La Paz

Madrid, , Spain

Site Status

Hospital Universitario Virgen de la Victoria

Málaga, , Spain

Site Status

Hospital Son Llatzer

Palma de Mallorca, , Spain

Site Status

Hospital Universitario de Salamanca

Salamanca, , Spain

Site Status

Hospital Universitario Virgen Del Rocio

Seville, , Spain

Site Status

Hospital Universitario La Fe

Valencia, , Spain

Site Status

Gazi Universitesi Tip Fakltesi

Ankara, , Turkey (Türkiye)

Site Status

Akdeniz Universitesi Tip Fakultesi

Antalya, , Turkey (Türkiye)

Site Status

Istanbul Universitesi Istanbul

Istanbul, , Turkey (Türkiye)

Site Status

Dokuz Eylul Universitesi Tip Faiultesi

Izimir, , Turkey (Türkiye)

Site Status

Royal Bournemouth Hospital

Bournemouth, , United Kingdom

Site Status

University Hospital of Wales

Cardiff, , United Kingdom

Site Status

Saint James University Hospital

Leeds, , United Kingdom

Site Status

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

London, , United Kingdom

Site Status

King's College Hospital

London, , United Kingdom

Site Status

Christie Hospital

Manchester, , United Kingdom

Site Status

John Radcliffe Hospital

Oxford, , United Kingdom

Site Status

Countries

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United States Australia Austria Belgium Canada Czechia France Germany Israel Italy Japan Poland Portugal Spain Turkey (Türkiye) United Kingdom

References

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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.

Reference Type RESULT
PMID: 27354480 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32064987 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29322849 (View on PubMed)

Other Identifiers

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CC-5013-MDS-005

Identifier Type: -

Identifier Source: org_study_id

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