Clinical trial NCT00064974: Efficacy and Safety Study of CC-5013 Monotherapy in Subjects With Myelodysplastic Syndromes
Official title: A Multicenter, Single-Arm, Open-Label Study of the Efficacy and Safety of CC-5013 Monotherapy in Subjects With Myelodysplastic Syndromes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myelodysplastic Syndromes
Keywords: MDS
CC-5013
Revlimid
Celgene
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2003-07-17
Enrollment: 215
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: RBC Transfusion Independence
Secondary outcomes:
measure: ≥ 50% decrease in RBC transfusion requirement
measure: Platelet Response
measure: Neutrophil Response
measure: Bone marrow Response
measure: Duration of Response
measure: Hemoglobin concentration
measure: Number of Participants with Adverse Event
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Arizona Cancer Center
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Tucson
country: United States
facility: Arizona Cancer Center
state: Arizona
city: Berkeley
country: United States
facility: Alta Bates Cancer Center
state: California
city: Rancho Mirage
country: United States
facility: Desert Hematology Oncology Medical Group, Inc.
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Lecanto
country: United States
facility: Cancer & Blood Disease Center
state: Florida
city: Miami
country: United States
facility: University of Miami- Sylvester Comp Cancer Center
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Marietta
country: United States
facility: Northwest Georgia Oncology - Wellstar Cancer Research
state: Georgia
city: Chicago
country: United States
facility: Rush Presbyterian-St. Luke's Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Skokie
country: United States
facility: Midwest Cancer Research Group
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Medical Center
state: Indiana
city: Baltimore
country: United States
facility: Johns Hopkins Oncology Center
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University School of Medicine
state: Michigan
city: Duluth
country: United States
facility: St. Luke's Oncology and Hematology Associates
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: New York
country: United States
facility: St. Vincents Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: New York Hospital- Cornell
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Mt. Sinai Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester-James P. Wilmot Cancer Center
state: New York
city: Winston Salem
country: United States
facility: Wake Forest University School of Medicine
state: North Carolina
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Portland
country: United States
facility: Kaiser Permanente Northwest Region
state: Oregon
city: Philadelphia
country: United States
facility: Drexel University College of Medicine
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Western Pennsylvania Cancer Institute
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital - SA Pathology Haematology
state: South Australia
city: Brisbane
country: Australia
facility: Princess Alexandra Hospital - Haematology
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital - Institute of Haematology
city: East Melbourne
country: Australia
facility: Peter McCallum Cancer Institute - Directorate of Cancer Medecine
city: Frankston
country: Australia
facility: Frankston Hospital-peninsula Health - Oncology Day Unit
city: Melbourne
country: Australia
facility: The Alfred Hospital - malignant haematology & stem cell transplantation
city: Waratah
country: Australia
facility: Calvary Mater Newcastle - Haematology
city: Wodonga
country: Australia
facility: Border Medical Oncology
city: Wollongong
country: Australia
facility: Wollongong Hospital - Haematology
city: Gent
country: Belgium
facility: UZ Gent - Hematology
city: Leuven
country: Belgium
facility: University Hospital Leuven - Hematology
city: Yvoir
country: Belgium
facility: Cliniques Universitaires ULC de Mont-Godinne - Hematology
city: Hradec Kralove
country: Czech Republic
facility: Fakultní nemocnice Hradec Králové - Hematology
city: Prague
country: Czech Republic
facility: Charles university Hospital - Internal Medicine
city: Aalborg
country: Denmark
facility: Aalborg Sygemus - Haematology
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
city: Vejle
country: Denmark
facility: Vejle Hospital - Hematology
city: Angers
country: France
facility: CHU Angers - Service des maladies du sang
city: Bayonne
country: France
facility: Centre Hospitalier de la côte basque - Hematologie
city: La Roche sur Yon
country: France
facility: Centre Hospitalier Départemental Vendée - Onco-hematologie
city: Lille
country: France
facility: CHRU de Lille - Service des maladies du sang
city: Marseille
country: France
facility: Institut Paoli Calmette - Hematology 1
city: Nantes
country: France
facility: CHU Hôtel-Dieu - Hematologie
city: Paris
country: France
facility: Hôpital Saint Louis - Immuno-hematologie
city: Paris
country: France
facility: CHU Saint Antoine - Service des maladies du sang
city: Pessac
country: France
facility: CHRU - Hôpital du Haut Lévêque - Centre François Magendie
city: Pierre-Benite
country: France
facility: Centre Hospitalier Lyon sud - Hematologie
city: Toulouse
country: France
facility: CHRU Hôpital Purpan - Hematologie
city: Tours
country: France
facility: Hôpital Bretonneau - Hématologie & Thérapie cellulaire
city: Vandoeuvre-les-Nancy
country: France
facility: CHU Nancy - Hematologie
city: Essen
country: Germany
facility: Universitätsklinikum Essen, Klinik für Hämatologie
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg - Medizinische Klinik und Poliklinik V
city: Jena
country: Germany
facility: Universitätsklinikum Jena - Klinik fur Innere Medizin II-Hamatologie/Onkologie
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig - Medizinische Klinik und Poliklinik II
city: Münster
country: Germany
facility: Universitätsklinikum Münster - Medizinische Klinik und Poliklinik A
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen - Medizinische Klinik und Poliklinik - Abteilung II
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm - Klinik fur Innere Medizin III
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg - Medizinische Klinik und Poliklinik II
city: Athens
country: Greece
facility: University of Athens - Alexandra Hospital; Clinical Therapeutics
city: Bologna
country: Italy
facility: Università degli Studi di Bologna - Policlinico S. Orsola - Hematology
city: Genova
country: Italy
facility: AO Universitaria San Martino - hematooncology
city: Napoli
country: Italy
facility: Fondazione "G. Pascale" - Hematology
city: Orbassano
country: Italy
facility: Ospedale San Luigi AO Luigi Gonzaga - Hematology
city: Padova
country: Italy
facility: Universita degli Studi di Padova - Clinical & Experimental Medicine
city: Piacenza
country: Italy
facility: Ospedale Guglielmo da Saliceto - hematooncology
city: Reggio Emilia
country: Italy
facility: Unità di Ematologia Arcispedale S. Maria Nuova - Haematology
city: Roma
country: Italy
facility: Policlinico Umberto I, Università "La Sapienza" di Roma - Hematology
city: Torino
country: Italy
facility: A.O.U. San Giovanni Battista - Hematology
city: Amsterdam
country: Netherlands
facility: VUMC - Hematology
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center - Hematology
city: Utrecht
country: Netherlands
facility: University Medical Center - Hematology
city: Moscow
country: Russian Federation
facility: Medical Sciences - Hematology & BMT
city: Moscow
country: Russian Federation
facility: Moscow State Medical Institution Municipal Clinical Hospital n.a. S.P. Botkin - Hematology
city: St. Petersburg
country: Russian Federation
facility: Russian Research Institute of Hematology and Blood Transfusion - Hematology
city: St. Petersburg
country: Russian Federation
facility: State Higher Educational Institution St. Petersburg State Medical University - Onco-hematology
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol - Hematology
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona - Hematology
city: Guipúzcoa
country: Spain
facility: Hospital de Donostia - Hematology
city: Madrid
country: Spain
facility: Hospital de La Princesa - Hematology
city: Madrid
country: Spain
facility: Hospital 12 de Octubre - Hematology
city: Salamanca
country: Spain
facility: Hospital de Salamanca - Hematology
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla - Hematology
city: Valencia
country: Spain
facility: Hospital La Fe - Hematology
city: Goteborg
country: Sweden
facility: Sahlgrenska Hospital, University of Goteborg - Hematology
city: Stockholm
country: Sweden
facility: Karolinska University Hospital Huddinge - Center of hematology
city: Stockholm
country: Sweden
facility: Karolinska University Hospital Solna- medicine
city: Uppsala
country: Sweden
facility: Overlakare Medocomcentrum - Hematology
city: Bern
country: Switzerland
facility: Inselspital, Institut für Medizinische Onkologie
city: Genève
country: Switzerland
facility: Hôpitaux Universitaire de Genève - Oncologie
city: Zurich
country: Switzerland
facility: Klinik und Poliklinik für Onkologie - UniversitätsSpital Zürich
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital - Haematology
city: Leeds
country: United Kingdom
facility: St James's University Hospital - Haematology
city: London
country: United Kingdom
facility: St Bartholomew's Hospital - Medical Oncology
city: London
country: United Kingdom
facility: King's College Hospital - Haematology Clinical Trials
city: Newcastle Upon Tyne
country: United Kingdom
facility: Freeman Hospital - Northern Centre for Cancer Care
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital - Centre for Clinical Haematology
city: Plymouth
country: United Kingdom
facility: Derriford Hospital - Haematology
city: Sheffield
country: United Kingdom
facility: Royal hallamshire Hospital - Haematology
city: Surrey
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust - Haematology
city: Wolverhampton
country: United Kingdom
facility: Royal Wolverhampton hospitals trust - Research and development
Study officials:
affiliation: Celgene Corporation
name: Robert Knight, MD
role: STUDY_DIRECTOR
References:
citation: 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.