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

Myelodysplastic Syndromes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00064974
• Other study ID #: CC-5013-MDS-002
• Status: Completed
• Phase: Phase 2
• First received: July 16, 2003
• Last updated: April 3, 2013
• Start date: June 2003
• Est. completion date: February 2007

Study information

• Verified date: April 2013
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Other known NCT identifiers

• NCT00077506

Recruitment information / eligibility

• Status: Completed
• Enrollment: 215
• Est. completion date: February 2007
• Est. primary completion date: January 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• CC-5013
CC-5013 10 mg (two 5 mg capsules) daily on days 1-28 every 28 days (28 day cycles)

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Celgene Corporation

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Czech Republic,  Denmark,  France,  Germany,  Greece,  Italy,  Netherlands,  Russian Federation,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	RBC Transfusion Independence			No
Secondary	= 50% decrease in RBC transfusion requirement			No
Secondary	Platelet Response	Platelet Response		No
Secondary	Neutrophil Response	Neutrophil Response		No
Secondary	Bone marrow Response	Bone marrow Response		No
Secondary	Duration of Response	Duration of Response		No
Secondary	Hemoglobin concentration	Change of hemoglobin concentration from baseline		No
Secondary	Number of Participants with Adverse Event	Number of Participants with Adverse Event		Yes