Lenalidomide Versus Placebo in Myelodysplastic Syndromes With a Deletion 5q[31] Abnormality

NCT00179621 | Completed Phase 3 Results DMC

• 2 other identifiers: CC-5013-MDS-0042005-000454-73
• Study Type: interventional
• Target: 205
• Locations: 9 countries
• Sites: 38

Brief Summary

The purpose of this study was to compare 2 doses (10 mg and 5 mg) of lenalidomide to that of placebo in subjects with red blood cell (RBC) transfusion-dependent low- or intermediate-1-risk IPSS MDS associated with a deletion (del) 5q\[31\] cytogenetic abnormality. Study participants were randomized to one of the two treatment groups or to placebo and took the study drug for 16 weeks. At this timepoint, participants were evaluated for erythroid response. If participants did not achieve at least a minor erythroid response, they were discontinued from the Double-Blind phase and entered into the Open-Label phase. All erythroid responders at Week 16 were to continue in the Double-Blind phase for up to 52 weeks. For participants that were still responding at the end of Double-Blind phase, they could then rollover into the Open-Label phase for an additional two years. Participants could remain on study for up to a total of 3 years. All participants who discontinued from the study were followed every 4 months for overall survival and progression to acute myeloid leukemia (AML).

Conditions

Myelodysplastic Syndromes

Keywords

MDS; transfusion dependent; anaemia; cytogenetic abnormality 5q-; erythroid response; leukaemia; CC-5013; Celgene; revlimid; lenalidomide

Outcome Measures

Primary Outcomes (1)

• Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence for >= 26 Weeks (182 Days)

  The count of study participants who had no RBC transfusions for 26 consecutive weeks or more during the double-blind period.

  Up to 52 weeks

Secondary Outcomes (14)

• Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence for 56 Days

  Up to 52 weeks

• Duration of Red Blood Cell (RBC) Transfusion Independence for Participants Who Became RBC Transfusion Independent for at Least 182 Days

  up to 3 years

• Maximum Change From Baseline in Hemoglobin During the Double-blind Period for Participants Who Became Red Blood Cell (RBC) Transfusion Independent for at Least 182 Days

  Baseline, up to 52 weeks

• Participants' Response in Platelet Counts as Defined by the International MDS Working Group (IWG 2000) During Double-blind Period

  up to 52 weeks

• Participants' Response in Absolute Neutrophil Counts as Defined by the International MDS Working Group (IWG 2000) During Double-blind Period

  up to week 52

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Placebo matching to active study arms.

Drug: Placebo

Lenalidomide 5 mg

EXPERIMENTAL

Lenalidomide 5 mg daily 28/28 days

Drug: Lenalidomide 5 mg

Lenalidomide 10 mg

EXPERIMENTAL

Lenalidomide 10 mg daily 21/28 days

Drug: Lenalidomide 10 mg

Interventions

Lenalidomide 5 mg DRUG

Lenalidomide 5 mg daily 28/28 days

Also known as: Revlimid

Lenalidomide 5 mg

Lenalidomide 10 mg DRUG

Lenalidomide 10 mg daily 21/28 days

Also known as: Revlimid

Lenalidomide 10 mg

Placebo DRUG

Placebo, matching to active study drug arms

Placebo

Eligibility Criteria

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

You may qualify if:

• Must understand and voluntarily sign an informed consent form
• Age 18 years at the time of signing the informed consent form
• Documented diagnosis of myelodysplastic syndromes (MDS) that meets International Prognostic Scoring System (IPSS) criteria for low to intermediate-1-risk disease and has an associated del 5q(31) cytogenetic abnormality
• Red blood cell (RBC) transfusion dependent anaemia defined as not having any 56 days without a RBC transfusion within at least the immediate 112 days
• Must be able to adhere to the study visit schedule and other protocol requirements

You may not qualify if:

• Pregnant or lactating females
• Prior therapy with lenalidomide
• Proliferative (white blood cell (WBC)= 12,000/mL) chronic myelomonocytic leukemia (CMML)
• Prior \>= grade-2 (using the National Cancer Institute (NCI)'s Common Terminology Criteria for AEs (CTCAE) (v 3.0)) allergic reaction to thalidomide
• Prior desquamating (blistering) rash while taking thalidomide
• Prior history of malignancy other than MDS (except basal cell or squamous cell carcinoma or carcinoma in situ of the cervix or breast) unless the subject has been free of disease for \>3 years
• Use of cytotoxic chemotherapeutic agents or experimental agents (agents that are not commercially available) for the treatment of MDS within 28 days
• Less than 6 months since prior allogeneic bone marrow transplantation
• Less than 3 months since prior autologous bone marrow or stem cell transplantation
• Less than 28 days since prior myelosuppressive anticancer biologic therapy
• Recombinant human erythropoietin (rHuEPO) therapy received within 28 days
• Known human immunodeficiency virus (HIV-1) positivity
• Any serious medical condition or psychiatric illness that will prevent the subject from signing the informed consent form or will place the subject at unacceptable risk if he or she participates in the study

Sponsors & Collaborators

• Celgene Corporation: lead
• ICON Clinical Research: collaborator

Study Sites (38)

AZ St-Jan Brugge AV

Bruges, 8000, Belgium

Location

UZ Gent

Ghent, 900, Belgium

Location

UZ Gasthuisberg

Leuven, 3000, Belgium

Location

CHU Mont Godine

Yvoir, 5530, Belgium

Location

Institut Paoli-Calmettes

Marseille, Cedex 9, B.P.156 - 13272, France

Location

CHU d'Angers Service des Maladies du Sang

Angers, 49933, France

Location

Hopital Avicenne

Bobigny, France

Location

CHRU Lille Service des Maladies du Sang

Lille, 59037, France

Location

CHU Nantes Hematologie et Medicine interne

Nantes, 44093, France

Location

CHU Archet 1Hematologie Clinique

Nice, 06202, France

Location

Hôpital Cochin Hematologie Clinique

Paris, 75014, France

Location

Centre Jean Bernhard Service Onco-Hematologie

Poitiers, 86021, France

Location

Centre Henri Becquerel Service d'Hematologie Clinique

Rouen, 76038, France

Location

CHU Purpan, Place du Dr Baylac, Pavillon des Médecines

Toulouse, 31059, France

Location

CHU Purpan, Place du Dr. Baylac, Pavillion des Medecines

Toulouse, 31059, France

Location

CHU Nancy Hematologie et Medecine interne

Vandœuvre-lès-Nancy, 54511, France

Location

Universitaetsklinikum Carl Gustav Carus

Dresden, 01307, Germany

Location

St Johannes Hospital

Duisburg, 47166, Germany

Location

Universitaetsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Hannover Medical School

Hanover, D-30625, Germany

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

Ospedale Niguarda Ca Granda

Milan, 20162, Italy

Location

University of Pavia Division of Hematology

Pavia, 27100, Italy

Location

University of Medical Centre

Nijmegen, 6526 GA, Netherlands

Location

Hematologie Erasmus MC

Rotterdam, 3000CA, Netherlands

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario La Fe

Valencia, 46009, Spain

Location

SU/Sahlgrenska Section of Hematology & Coagulation

Gothenburg, SE 413 45, Sweden

Location

Department of Medicine University Hospital

Lund, S-221 85, Sweden

Location

Korolinska Institutet Department of Hematology

Stockholm, 14186, Sweden

Location

University Hospital of Wales, Dept of Haematology

Cardiff, Wales, CF14 4XW, United Kingdom

Location

Leed General Infirmary

Leeds, West Yorkshire, LS1 3 EX, United Kingdom

Location

The Royal Bournemouth Hospital

Bournemouth, BH7 7DW, United Kingdom

Location

Ninewells Hospital and Medical School

Dundee, DD1 9SY, United Kingdom

Location

Kings College Hospital, Denmark Hill

London, SE 5 9RS, United Kingdom

Location

Central Manchester and Manchester Children's University Hospitals NHS Trust

Manchester, M13 9WL, United Kingdom

Location

Nottingham City Hospital

Nottingham, NG5 1PB, United Kingdom

Location

John Radcliffe Hospital and the Weatherall Institute of Molecular Medicine

Oxford, OX3 9DS, United Kingdom

Location

Related Publications (10)

• Fenaux, Pierre, Giagounidis, Aristotle, Selleslag, Dominik, Beyne-Rauzy, Odile, Mufti, Ghulam J, Mittelman, Moshe, Muus, Petra, te Boekhorst, Peter, Sanz, Guillermo, del Canizo, Consuelo, Guerci-Bresler, Agnes, Schlegelberger, Brigitte, Aul, Carlo, Kreipe, Hans, Goehring, Gudrun, Knight, Robert, Francis, John, Fu, Tommy, Hellstrom-Lindberg, Eva. RBC Transfusion Independence and Safety Profile of Lenalidomide 5 or 10 mg in Pts with Low- or Int-1-Risk MDS with Del5q: Results From a Randomized Phase III Trial (MDS-004). ASH Annual Meeting Abstracts 2009 114: 944.

  RESULT

• Fenaux, P., Giagounidis, A., Selleslag, D. L., Beyne-Rauzy, O., Mittelman, M., Muus, P., Knight, R. D., Fu, T., Hellstrom-Lindberg, E., The MDS-004 Len del(5q) Study Group. Safety of lenalidomide (LEN) from a randomized phase III trial (MDS-004) in low-/int-1-risk myelodysplastic syndromes (MDS) with a del(5q) abnormality. J Clin Oncol (Meeting Abstracts) 2010 28: 6598

  RESULT

• Fenaux, P., Giagounidis, A., Selleslag, D., Knight, R., Fu, T., Hellström-Lindberg, E. Effect of baseline EPO and prior erythropoiesis stimulating agents on RBC transfusion independence in Low-/Int-1-Risk MDS with del 5q treated with lenalidomide: A randomized phase 3 study (MDS-004). Haematologica 2010; 95[suppl.2]:125, abs. 0311.

  RESULT

• Brandenburg, N., Fu, T., Revicki, D., Knight, R., Muus, P., Fenaux, P. Impact of lenalidomide on health-related quality of life in patients with RBC transfusion-dependent low- or int-1-risk myelodysplastic syndromes with del 5q: a randomized Phase 3 study (MDS-004). Haematologica 2010; 95[suppl.2]:127, abs. 0316

  RESULT

• Fenaux, P., Giagounidis, A., Beyne-Rauzy, O., Mufti, G., Mittelman, M., Muus, P., te Boekhorst, P., Sanz, G., Cazzola, M., Backstrom, J., Fu, T., Hellström-Lindberg, E. Prognostic Factors of Long-Term Outcomes In Low- or Int-1-Risk MDS with del5q Treated with Lenalidomide (LEN): Results From a Randomized Phase 3 Trial (MDS-004). Blood ASH Annual Meeting Abstracts 2010 116:21 abs. 4027.

  RESULT

• Brandenburg, N., Yu, R., Revicki, D. Reliability and Validity of the FACT-AN In Patients with Low or Int-1-Risk Myelodysplastic Syndromes with Deletion 5q. Blood ASH Annual Meeting Abstracts 2010 116:21 abs. 3827.

  RESULT

• Fenaux P, Giagounidis A, Selleslag D, Beyne-Rauzy O, Mittelman M, Muus P, Nimer SD, Hellstrom-Lindberg E, Powell BL, Guerci-Bresler A, Sekeres MA, Deeg HJ, Del Canizo C, Greenberg PL, Shammo JM, Skikne B, Yu X, List AF. Clinical characteristics and outcomes according to age in lenalidomide-treated patients with RBC transfusion-dependent lower-risk MDS and del(5q). J Hematol Oncol. 2017 Jun 26;10(1):131. doi: 10.1186/s13045-017-0491-2.

  PMID: 28651604 DERIVED

• Saft L, Karimi M, Ghaderi M, Matolcsy A, Mufti GJ, Kulasekararaj A, Gohring G, Giagounidis A, Selleslag D, Muus P, Sanz G, Mittelman M, Bowen D, Porwit A, Fu T, Backstrom J, Fenaux P, MacBeth KJ, Hellstrom-Lindberg E. p53 protein expression independently predicts outcome in patients with lower-risk myelodysplastic syndromes with del(5q). Haematologica. 2014 Jun;99(6):1041-9. doi: 10.3324/haematol.2013.098103. Epub 2014 Mar 28.

  PMID: 24682512 DERIVED

• Fenaux P, Giagounidis A, Selleslag D, Beyne-Rauzy O, Mufti G, Mittelman M, Muus P, Te Boekhorst P, Sanz G, Del Canizo C, Guerci-Bresler A, Nilsson L, Platzbecker U, Lubbert M, Quesnel B, Cazzola M, Ganser A, Bowen D, Schlegelberger B, Aul C, Knight R, Francis J, Fu T, Hellstrom-Lindberg E; MDS-004 Lenalidomide del5q Study Group. A randomized phase 3 study of lenalidomide versus placebo in RBC transfusion-dependent patients with Low-/Intermediate-1-risk myelodysplastic syndromes with del5q. Blood. 2011 Oct 6;118(14):3765-76. doi: 10.1182/blood-2011-01-330126. Epub 2011 Jul 13.

  PMID: 21753188 DERIVED

• Gohring G, Giagounidis A, Busche G, Hofmann W, Kreipe HH, Fenaux P, Hellstrom-Lindberg E, Schlegelberger B. Cytogenetic follow-up by karyotyping and fluorescence in situ hybridization: implications for monitoring patients with myelodysplastic syndrome and deletion 5q treated with lenalidomide. Haematologica. 2011 Feb;96(2):319-22. doi: 10.3324/haematol.2010.026658. Epub 2010 Nov 25.

  PMID: 21109690 DERIVED

MeSH Terms

Conditions

Myelodysplastic Syndromes; Anemia; Leukemia

Interventions

Lenalidomide

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms by Histologic Type; Neoplasms

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: Associate Director, Clinical Trials Disclosure
• Organization: Celgene Corporation

clinicaltrialdisclosure@celgene.com

1-888-260-1599

Study Officials

• Jay Backstrom, 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: CROSSOVER
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: September 10, 2005
• First Posted: September 16, 2005
• Study Start: July 1, 2005
• Primary Completion: June 1, 2008
• Study Completion: June 1, 2010
• Last Updated: April 14, 2011
• Results First Posted: March 17, 2011

Record last verified: 2011-04

Locations

NL (2); GB (8); DE (4); SE (3); IL (1); FR (12); IT (2); BE (4); ES (2)