Lenalidomide Safety/Efficacy in Myelodysplastic Syndromes (MDS) Associated With a Deletion (Del)(5q) Cytogenetic Abnormality

NCT ID: NCT00065156

Last Updated: 2019-11-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 148 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-06-01
• Study Completion Date: 2008-08-01

Brief Summary

This study is a multicenter, single-arm, open-label study of oral lenalidomide monotherapy administered to red blood cell (RBC) transfusion-dependent subjects with low- or intermediate-1-risk Myelodysplastic Syndromes (MDS) associated with a del (5q31-33) cytogenetic abnormality. Screening procedures will take place within 28 days of the first day of lenalidomide treatment. Subjects will receive lenalidomide in 28-day cycles for up to 6 cycles, or until bone marrow disease progression or progression/relapse following erythroid hematologic improvement 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.

Conditions

Myelodysplastic Syndromes

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Lenalidomide

Group Type: EXPERIMENTAL

lenalidomide

Intervention Type: DRUG

10 mg orally once daily for 21 days out of a 28-day cycle (syncopated); subsequently amended (Amendment 1, dated 27 August 2003) to employ a continuous dosage regimen in which 10 mg was taken once daily for 28 day cycles (continuous). Subjects who initially began a syncopated regimen and who did not experience a dose-limiting adverse event were allowed to switch to the continuous regimen.

Interventions

lenalidomide

10 mg orally once daily for 21 days out of a 28-day cycle (syncopated); subsequently amended (Amendment 1, dated 27 August 2003) to employ a continuous dosage regimen in which 10 mg was taken once daily for 28 day cycles (continuous). Subjects who initially began a syncopated regimen and who did not experience a dose-limiting adverse event were allowed to switch to the continuous regimen.

Intervention Type: DRUG

Other Intervention Names

CC-5013

Eligibility Criteria

Inclusion Criteria

• Must understand and voluntarily sign an informed consent form
• Age 18 years or older at the time of signing the informed consent
• Must be able to adhere to the study visit schedule and other protocol requirements.
• Diagnosis of low or intermediate-1-risk International Prognostic Scoring System (IPSS) Myelodysplastic Syndromes (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 greater than or equal to 2 units of RBCs within 8 weeks of the first day of study drug treatment.
• Eastern Cooperative Oncology Group (ECOG) 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 cell/mm^3 (0.5*10^9/L)
• Lab Abnormality: Platelet count <50,000/mm^3 (50*10^9/L)
• Lab Abnormality: Serum creatinine >2.5 mg/dL (221 mmol/L)
• Lab Abnormality: Serum total bilirubin >2.0 mg/dL (34 mmol/L)
• Prior greater than or equal to grade 3 National Cancer Institute (NCI) Common Toxicity Criteria (CTC) allergic reaction/hypersensitivity to 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.
• Prior greater than or equal to grade 3 NCI CTC rash or any desquamation (blistering) while taking thalidomide.
• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celgene

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alan F List, MD

Role: PRINCIPAL_INVESTIGATOR

H. Lee Moffitt Cancer Center and Research Institute

Locations

Arizona Cancer Center

Scottsdale, Arizona, United States

Mayo Clinic

Scottsdale, Arizona, United States

Arizona Cancer Center

Tucson, Arizona, United States

Desert Hematology & Oncology Medical Group

Rancho Mirage, California, United States

Stanford University Medical Center

Stanford, California, United States

Mayo Clinic

Jacksonville, Florida, United States

Cancer & Blood Disease Center

Lecanto, Florida, United States

University of Miami Sylvester Comp Cancer Center

Miami, Florida, United States

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Northwest Georgia Oncology - Wellstar Cancer Research

Marietta, Georgia, United States

Rush-Presbyterian- St. Luke's Medical Center

Chicago, Illinois, United States

University of Chicago Medical Center

Chicago, Illinois, United States

Midwest Cancer Research Group

Skokie, Illinois, United States

Johns Hopkins Oncology Center

Baltimore, Maryland, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Wayne State University School of Medicine

Detroit, Michigan, United States

Mayo Clinic

Rochester, Minnesota, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

New York Hospital-Cornell

New York, 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

University of Rochester- James P. Wilmot Cancer Center

Rochester, New York, United States

Wake Forest University School of Medicine

Winston-Salem, North Carolina, United States

The Cleveland Clinic Foundation

Cleveland, Ohio, United States

Oregon Health & Science University

Portland, Oregon, United States

Kaiser Permanente Northwest Region

Portland, Oregon, United States

Western Pennsylvania Cancer Institute

Pittsburgh, Pennsylvania, United States

MD Anderson Cancer Center

Houston, Texas, United States

Swedish Cancer Institute

Seattle, Washington, United States

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

St. Johannes Hospital

Duisburg, , Germany

Countries

United States; Germany

References

Sekeres MA, Maciejewski JP, Giagounidis AA, Wride K, Knight R, Raza A, List AF. Relationship of treatment-related cytopenias and response to lenalidomide in patients with lower-risk myelodysplastic syndromes. J Clin Oncol. 2008 Dec 20;26(36):5943-9. doi: 10.1200/JCO.2007.15.5770. Epub 2008 Nov 17.

Reference Type: BACKGROUND

PMID: 19018091 (View on PubMed)

Prebet T, Cluzeau T, Park S, Sekeres MA, Germing U, Ades L, Platzbecker U, Gotze K, Vey N, Oliva E, Sugrue MM, Bally C, Kelaidi C, Al Ali N, Fenaux P, Gore SD, Komrokji R. Outcome of patients treated for myelodysplastic syndromes with 5q deletion after failure of lenalidomide therapy. Oncotarget. 2017 Jun 14;8(47):81926-81935. doi: 10.18632/oncotarget.18477. eCollection 2017 Oct 10.

Reference Type: BACKGROUND

PMID: 29137233 (View on PubMed)

List A, Dewald G, Bennett J, Giagounidis A, Raza A, Feldman E, Powell B, Greenberg P, Thomas D, Stone R, Reeder C, Wride K, Patin J, Schmidt M, Zeldis J, Knight R; Myelodysplastic Syndrome-003 Study Investigators. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med. 2006 Oct 5;355(14):1456-65. doi: 10.1056/NEJMoa061292.

Reference Type: RESULT

PMID: 17021321 (View on PubMed)

A.F. List, et.al. Results of the MDS-002 and -003 international phase II studies evaluating lenalidomide (CC-5013; Revlimid) in the treatment of transfusion-dependent (TD) patients with myelodysplastic syndrome (MDS). European Hematology Association 10th Conference June 2-5, 2005 Abstract #0772

Reference Type: 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.

Reference Type: DERIVED

PMID: 28651604 (View on PubMed)

Other Identifiers

CC-5013-MDS-003

Identifier Type: -

Identifier Source: org_study_id

NCT00074126

Identifier Type: -

Identifier Source: nct_alias