Clinical trial NCT00065156: Lenalidomide Safety/Efficacy in Myelodysplastic Syndromes (MDS) Associated With a Deletion (Del)(5q) Cytogenetic Abnormality
Official title: A Multicenter, Single-arm, Open-label Study of the Efficacy and Safety of Lenalidomide Monotherapy in Red Blood Cell Transfusion-dependent Subjects With Myelodysplastic Syndromes Associated With a Del(5q) Cytogenetic Abnormality.
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: 2003-07-18
Enrollment: 148
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Participants Who Achieved Red Blood Cell (RBC) -Transfusion Independence
timeFrame: Up to 2 years
Secondary outcomes:
measure: Participants With Adverse Experiences
timeFrame: Up to 2 Years
measure: Participants With a >= 50% Decrease From Baseline in Red Blood Cell (RBC) Transfusion Requirements Over Any Consecutive 56 Days During Study
timeFrame: Baseline (Day -54 to Day 0), During study (Day 1 up to 2 years)
measure: Time to Transfusion Independence
timeFrame: up to 2 years
measure: Participants Who Relapsed or Maintained Their Transfusion Independence After Achieving Transfusion Independence During the Study
timeFrame: up to 2 years
measure: Kaplan Meier Estimate for Duration of Transfusion Independence Response
timeFrame: up to 2 years
measure: Change in Hemoglobin Concentration From Baseline to Maximum Value During Response Period for Responders
timeFrame: Baseline (Day -54 to Day 0), During study (Day 1 up to 2 years)
measure: Participant Counts of Cytogenetic Response
timeFrame: up to 2 years
measure: Participant Counts of Platelet Response
timeFrame: up to 2 years
measure: Participant Counts of Absolute Neutrophil Count (ANC) Response
timeFrame: up to 2 years
measure: Participants With Complete or Partial Bone Marrow Improvement
timeFrame: up to 2 years
measure: Participants With Bone Marrow Progression
timeFrame: up to 2 years
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: Rancho Mirage
country: United States
facility: Desert Hematology & Oncology Medical Group
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
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: 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: 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: 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: 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: Duisburg
country: Germany
facility: St. Johannes Hospital
Study officials:
affiliation: H. Lee Moffitt Cancer Center and Research Institute
name: Alan F List, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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
citation: 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.