Efficacy and Safety Study of CC-5013 Monotherapy in Subjects With Myelodysplastic Syndromes

A Multicenter, Single-Arm, Open-Label Study of the Efficacy and Safety of CC-5013 Monotherapy in Subjects With Myelodysplastic Syndromes

This study is a multi-center, single-arm, open-label study of oral CC-5013 monotherapy administered at a dose of 10 mg daily on Days 1-21 every 28 days (28-day cycles) to red blood cell (RBC) transfusion-dependent subjects with low- or intermediate-1-risk MDS who do not have a del (5q31-33) cytogenetic abnormality. Screening procedures will take place within 28 days of first day of study drug treatment. Subjects will receive study drug (CC-5013) in 28-day cycles for up to 6 cycles, or until bone marrow disease progression or progression/relapse following erythroid hematologic improvement (Appendix I) is documented. Study visits will occur every cycle (every 28 days) and laboratory monitoring to assess hematological parameters will occur every 14 days. Safety and efficacy assessments to be performed during the study are outlined in the Schedule of Study Assessments.

Study Overview

• Status: Completed
• Conditions: Myelodysplastic Syndromes
• Intervention / Treatment: Drug: CC-5013

• Study Type: Interventional
• Enrollment (Actual): 215
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Brisbane, Australia, 4102
    • Princess Alexandra Hospital - Haematology
  • Camperdown, Australia, 2050
    • Royal Prince Alfred Hospital - Institute of Haematology
  • East Melbourne, Australia, 3002
    • Peter McCallum Cancer Institute - Directorate of Cancer Medecine
  • Frankston, Australia, 3199
    • Frankston Hospital-Peninsula Health - Oncology Day Unit
  • Melbourne, Australia, 3004
    • The Alfred Hospital - Malignant Haematology & Stem Cell Transplantation
  • Waratah, Australia, 2298
    • Calvary Mater Newcastle - Haematology
  • Wodonga, Australia, 3690
    • Border Medical Oncology
  • Wollongong, Australia, 2500
    • Wollongong Hospital - Haematology
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital - SA Pathology Haematology
• Belgium
  • Gent, Belgium, 9000
    • UZ Gent - Hematology
  • Leuven, Belgium, 3000
    • University Hospital Leuven - Hematology
  • Yvoir, Belgium, 5530
    • Cliniques Universitaires ULC de Mont-Godinne - Hematology
• Czech Republic
  • Hradec Kralove, Czech Republic, 50005
    • Fakultní nemocnice Hradec Králové - Hematology
  • Prague, Czech Republic, 12808
    • Charles University Hospital - Internal Medicine
• Denmark
  • Aalborg, Denmark, 9000
    • Aalborg Sygemus - Haematology
  • Aarhus, Denmark, 8000
    • Aarhus University Hospital
  • Odense, Denmark, 5000
    • Odense University Hospital
  • Vejle, Denmark, 7100
    • Vejle Hospital - Hematology
• France
  • Angers, France, 49033
    • CHU Angers - Service des maladies du sang
  • Bayonne, France, 64019
    • Centre Hospitalier de la côte basque - Hematologie
  • La Roche sur Yon, France, 85925
    • Centre Hospitalier Départemental Vendée - Onco-hematologie
  • Lille, France, cedex 59037
    • CHRU de Lille - Service des maladies du sang
  • Marseille, France, cedex 13009
    • Institut Paoli Calmette - Hematology 1
  • Nantes, France, cedex 01 44093
    • CHU Hôtel-Dieu - Hematologie
  • Paris, France, 75010
    • Hôpital Saint Louis - Immuno-hematologie
  • Paris, France, cedex 12 75012
    • CHU Saint Antoine - Service des maladies du sang
  • Pessac, France, 33604
    • CHRU - Hôpital du Haut Lévêque - Centre François Magendie
  • Pierre-Benite, France, cedex 69495
    • Centre Hospitalier Lyon Sud - Hématologie
  • Toulouse, France, cedex 9 31059
    • CHRU Hôpital Purpan - Hematologie
  • Tours, France, cedex 37044
    • Hôpital Bretonneau - Hématologie & Thérapie cellulaire
  • Vandoeuvre-les-Nancy, France, 54511
    • CHU Nancy - Hematologie
• Germany
  • Essen, Germany, 45122
    • Universitätsklinikum Essen, Klinik für Hämatologie
  • Heidelberg, Germany, 69120
    • Universitätsklinikum Heidelberg - Medizinische Klinik und Poliklinik V
  • Jena, Germany, 7740
    • Universitätsklinikum Jena - Klinik fur Innere Medizin II-Hamatologie/Onkologie
  • Leipzig, Germany, 4103
    • Universitätsklinikum Leipzig - Medizinische Klinik und Poliklinik II
  • Münster, Germany, 48149
    • Universitätsklinikum Münster - Medizinische Klinik und Poliklinik A
  • Tübingen, Germany, 72076
    • Universitätsklinikum Tübingen - Medizinische Klinik und Poliklinik - Abteilung II
  • Ulm, Germany, 89081
    • Universitätsklinikum Ulm - Klinik fur Innere Medizin III
  • Würzburg, Germany, 97080
    • Universitätsklinikum Würzburg - Medizinische Klinik und Poliklinik II
• Greece
  • Athens, Greece, 14572
    • University of Athens - Alexandra Hospital; Clinical Therapeutics
• Italy
  • Bologna, Italy, 40138
    • Università degli Studi di Bologna - Policlinico S. Orsola - Hematology
  • Genova, Italy, 16132
    • AO Universitaria San Martino - hematooncology
  • Napoli, Italy, 80131
    • Fondazione "G. Pascale" - Hematology
  • Orbassano, Italy, 10043
    • Ospedale San Luigi AO Luigi Gonzaga - Hematology
  • Padova, Italy, 35128
    • Universita degli Studi di Padova - Clinical & Experimental Medicine
  • Piacenza, Italy, 29100
    • Ospedale Guglielmo da Saliceto - hematooncology
  • Reggio Emilia, Italy, 42100
    • Unità di Ematologia Arcispedale S. Maria Nuova - Haematology
  • Roma, Italy, 00161
    • Policlinico Umberto I, Università "La Sapienza" di Roma - Hematology
  • Torino, Italy, 10126
    • A.O.U. San Giovanni Battista - Hematology
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • VUMC - Hematology
  • Rotterdam, Netherlands, 3015 CE
    • Erasmus Medical Center - Hematology
  • Utrecht, Netherlands, 3584-CX
    • University Medical Center - Hematology
• Russian Federation
  • Moscow, Russian Federation, 125167
    • Medical Sciences - Hematology & BMT
  • Moscow, Russian Federation, 125284
    • Moscow State Medical Institution Municipal Clinical Hospital n.a. S.P. Botkin - Hematology
  • St. Petersburg, Russian Federation, 191024
    • Russian Research Institute of Hematology and Blood Transfusion - Hematology
  • St. Petersburg, Russian Federation, 197341
    • State Higher Educational Institution St. Petersburg State Medical University - Onco-hematology
• Spain
  • Badalona, Spain, 8916
    • Hospital Germans Trias i Pujol - Hematology
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial de Barcelona - Hematology
  • Guipúzcoa, Spain, 20014
    • Hospital de Donostia - Hematology
  • Madrid, Spain, 28006
    • Hospital de La Princesa - Hematology
  • Madrid, Spain, 28041
    • Hospital 12 de Octubre - Hematology
  • Salamanca, Spain, 37007
    • Hospital de Salamanca - Hematology
  • Santander, Spain, 39008
    • Hospital Universitario Marqués de Valdecilla - Hematology
  • Valencia, Spain, 46009
    • Hospital La Fe - Hematology
• Sweden
  • Goteborg, Sweden, S-41345
    • Sahlgrenska Hospital, University of Goteborg - Hematology
  • Stockholm, Sweden, 14152
    • Karolinska University Hospital Huddinge - Center of hematology
  • Stockholm, Sweden, 17176
    • Karolinska University Hospital Solna- medicine
  • Uppsala, Sweden, 75185
    • Overlakare Medocomcentrum - Hematology
• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital, Institut für Medizinische Onkologie
  • Genève, Switzerland, 1211
    • Hôpitaux Universitaire de Genève - Oncologie
  • Zurich, Switzerland, 8091
    • Klinik und Poliklinik für Onkologie - UniversitätsSpital Zürich
• United Kingdom
  • Bournemouth, United Kingdom, BH7 7DW
    • Royal Bournemouth Hospital - Haematology
  • Leeds, United Kingdom, LS9 7TF
    • St James's University Hospital - Haematology
  • London, United Kingdom, EC1A 7BE
    • St Bartholomew's Hospital - Medical Oncology
  • London, United Kingdom, SE5 9RS
    • King's College Hospital - Haematology Clinical Trials
  • Newcastle Upon Tyne, United Kingdom, NE7 7DN
    • Freeman Hospital - Northern Centre for Cancer Care
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham City Hospital - Centre for Clinical Haematology
  • Plymouth, United Kingdom, PL6 8DH
    • Derriford Hospital - Haematology
  • Sheffield, United Kingdom, S10 2JF
    • Royal hallamshire Hospital - Haematology
  • Surrey, United Kingdom, SM2 5PT
    • Royal Marsden NHS Foundation Trust - Haematology
  • Wolverhampton, United Kingdom, WV10 OQP
    • Royal Wolverhampton Hospitals Trust - Research and Development
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic
    • Scottsdale, Arizona, United States, 85258
      • Arizona Cancer Center
    • Tucson, Arizona, United States, 85724-5024
      • Arizona Cancer Center
  • California
    • Berkeley, California, United States, 94704
      • Alta Bates Cancer Center
    • Rancho Mirage, California, United States, 92270
      • Desert Hematology Oncology Medical Group, Inc.
    • Stanford, California, United States, 94305-5750
      • Stanford University Medical Center
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
    • Lecanto, Florida, United States, 34461
      • Cancer & Blood Disease Center
    • Miami, Florida, United States, 33136
      • University of Miami- Sylvester Comp Cancer Center
    • Tampa, Florida, United States, 33612-9497
      • H. Lee Moffitt Cancer Center and Research Institute
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Northwest Georgia Oncology - Wellstar Cancer Research
  • Illinois
    • Chicago, Illinois, United States, 60637-1470
      • University of Chicago Medical Center
    • Chicago, Illinois, United States, 60612-3515
      • Rush Presbyterian-St. Luke's Medical Center
    • Skokie, Illinois, United States, 60077
      • Midwest Cancer Research Group
  • Indiana
    • Indianapolis, Indiana, United States, 46202-5149
      • Indiana University Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21287-8963
      • Johns Hopkins Oncology Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115-6084
      • Dana-Farber Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48201-2097
      • Wayne State University School of Medicine
  • Minnesota
    • Duluth, Minnesota, United States, 55805
      • St. Luke's Oncology and Hematology Associates
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Nebraska
    • Omaha, Nebraska, United States, 68198-7680
      • University of Nebraska Medical Center
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • Mineola, New York, United States, 11501-3893
      • Winthrop University Hospital
    • New York, New York, United States, 10021
      • Memorial Sloan-Kettering Cancer Center
    • New York, New York, United States, 10011
      • St. Vincents Comprehensive Cancer Center
    • New York, New York, United States, 10029
      • Mt. Sinai Medical Center
    • New York, New York, United States, 10021-0034
      • New York Hospital- Cornell
    • Rochester, New York, United States, 14642
      • University of Rochester-James P. Wilmot Cancer Center
  • North Carolina
    • Winston Salem, North Carolina, United States, 27157-1082
      • Wake Forest University School of Medicine
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation
  • Oregon
    • Portland, Oregon, United States, 97227
      • Kaiser Permanente Northwest Region
    • Portland, Oregon, United States, 97201
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19129
      • Drexel University College of Medicine
    • Pittsburgh, Pennsylvania, United States, 15224
      • Western Pennsylvania Cancer Institute
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Institute
    • Seattle, Washington, United States, 98109-4417
      • Fred Hutchinson Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Must understand and voluntarily sign an informed consent form.
• Age ≥ 18 years at the time of signing the informed consent form.
• Must be able to adhere to the study visit schedule and other protocol requirements.
• Diagnosis of low - or intermediate-1-risk IPSS (Appendix III) MDS without an abnormality of chromosome 5 involving a deletion between bands q31 and q33.
• Red blood cell (RBC) transfusion-dependent anemia defined as having received ≥ to 2 units of RBCs within 8 weeks of the first day of study drug treatment.
• Eastern Cooperative Oncology Group (ECOG) (Appendix IV) performance status score of 0, 1, or 2.
• Women of childbearing potential (WCBP) must have a negative serum or urine pregnancy test within 7 days of starting study drug.
• Sexually active WCBP must agree to use adequate contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) while on study drug.
• WCBP must agree to have pregnancy tests every 4 weeks while on study drug.

Exclusion Criteria:

• Pregnant or lactating females.
• Prior therapy with lenalidomide.
• An abnormality of chromosome 5 involving a deletion between bands q31 and q33.
• Lab Abnormality: Absolute neutrophil count (ANC) <500 cells/mm3 (0.5 x 109/L)
• Lab Abnormality: Platelet count <50,000/mm3 (50 x 109/L)
• Lab Abnormality: Serum creatinine >2.5 mg/dL (221 mmol/L)
• Lab Abnormality: Serum glutamic oxaloacetic transaminase/Aspartate transaminase (SGOT/AST) or Serum glutamic pyruvic transaminase/Alanine transaminase (SGPT/ALT) >3.0 x upper limit of normal (ULN)
• Lab Abnormality: Serum total bilirubin >2.0 mg/dL (34 mmol/L)
• Prior ≥ grade 3 National Cancer Institute (NCI) Common Toxicity Criteria (CTC) (Appendix VI) allergic reaction/hypersensitivity to thalidomide.
• Prior ≥ grade 3 NCI CTC (Appendix VI) rash or any desquamation (blistering) while taking thalidomide.
• Clinically significant anemia due to factors such as iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis or gastrointestinal bleeding
• If a marrow aspirate is not evaluable for storage iron, transferrin saturation must be > 20 % and serum ferritin not less than 50 ng/mL.
• Use of hematopoietic growth factors within 7 days of the first day of study drug treatment.
• Chronic use (>2 weeks) of greater than physiologic doses of a corticosteroid agent (dose equivalent to >10 mg/day of prednisone) within 28 days of the first day of study drug treatment.
• Use of experimental or standard drugs (i.e. chemotherapeutic, immunosuppressive, and cytoprotective agents) for the treatment of MDS within 28 days of the first day of study drug treatment.
• 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 greater than or equal to 3 years.
• Use of any other experimental therapy within 28 days of the first day of study drug treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: CC-5013; CC-5013 10 mg (two 5 mg capsules) daily on days 1-28 every 28 days (28 day cycles)	Drug: CC-5013; CC-5013 10 mg (two 5 mg capsules) daily on days 1-28 every 28 days (28 day cycles); Other Names: lenalidomide

What is the study measuring?

Primary Outcome Measures

Outcome Measure
RBC Transfusion Independence

Secondary Outcome Measures

Outcome Measure	Measure Description
≥ 50% decrease in RBC transfusion requirement
Platelet Response	Platelet Response
Neutrophil Response	Neutrophil Response
Bone marrow Response	Bone marrow Response
Duration of Response	Duration of Response
Hemoglobin concentration	Change of hemoglobin concentration from baseline
Number of Participants with Adverse Event	Number of Participants with Adverse Event

Collaborators and Investigators

• Sponsor: Celgene Corporation

Publications and helpful links

General Publications

• Raza A, Reeves JA, Feldman EJ, Dewald GW, Bennett JM, Deeg HJ, Dreisbach L, Schiffer CA, Stone RM, Greenberg PL, Curtin PT, Klimek VM, Shammo JM, Thomas D, Knight RD, Schmidt M, Wride K, Zeldis JB, List AF. Phase 2 study of lenalidomide in transfusion-dependent, low-risk, and intermediate-1 risk myelodysplastic syndromes with karyotypes other than deletion 5q. Blood. 2008 Jan 1;111(1):86-93. doi: 10.1182/blood-2007-01-068833. Epub 2007 Sep 24.

Study record dates

Study Major Dates

• Study Start: June 1, 2003
• Primary Completion (ACTUAL): January 1, 2007
• Study Completion (ACTUAL): February 1, 2007

Study Registration Dates

• First Submitted: July 16, 2003
• First Submitted That Met QC Criteria: July 16, 2003
• First Posted (ESTIMATE): July 17, 2003

Study Record Updates

• Last Update Posted (ESTIMATE): April 4, 2013
• Last Update Submitted That Met QC Criteria: April 3, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: MDS; Revlimid; CC-5013; Celgene
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Lenalidomide
• Other Study ID Numbers: CC-5013-MDS-002