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

Myelodysplastic Syndromes Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00065156
• Other study ID #: CC-5013-MDS-003
• Status: Completed
• Phase: Phase 2
• Start date: June 1, 2003
• Est. completion date: August 1, 2008

Study information

• Verified date: November 2019
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Other known NCT identifiers

• NCT00074126

Recruitment information / eligibility

• Status: Completed
• Enrollment: 148
• Est. completion date: August 1, 2008
• Est. primary completion date: August 1, 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chromosome Aberrations
• Chromosome Disorders
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
Germany	St. Johannes Hospital	Duisburg
United States	Johns Hopkins Oncology Center	Baltimore	Maryland
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	MD Anderson Cancer Center	Houston	Texas
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	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	University of Nebraska Medical Center	Omaha	Nebraska
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	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

Countries where clinical trial is conducted

United States,  Germany, 

References & Publications (4)

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

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 syndr — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Participants Who Achieved Red Blood Cell (RBC) -Transfusion Independence	Number of participants who achieved RBC-transfusion independence, which was defined as the absence of an intravenous infusion of any RBC transfusion during any consecutive "rolling" 56 days during the treatment period (eg, Days 1 to 56, Days 2 to 57, Days 3 to 58, etc), and accompanied by at least a 1 g/dL increase from screening/baseline in hemoglobin.	Up to 2 years
Secondary	Participants With Adverse Experiences	Counts of study participants who had adverse events (AEs) during the study. A participant with multiple occurrences of an adverse event within a category is counted only once in that category. Adverse events were evaluated by the investigator.; The National Cancer Institute (NCI)'s Common Toxicity Criteria for AEs (NCI CTC) was used to grade AE severity. Severity grade 3= severe and undesirable AE. Severity grade 4= life-threatening or disabling AE.	Up to 2 Years
Secondary	Participants With a >= 50% Decrease From Baseline in Red Blood Cell (RBC) Transfusion Requirements Over Any Consecutive 56 Days During Study	A participant was categorized as having a transfusion reduction response if there was a = 50% decrease from pretreatment transfusion requirements (before the start of the study mediation) compared to any consecutive 56 days during the study (i.e. post treatment).	Baseline (Day -54 to Day 0), During study (Day 1 up to 2 years)
Secondary	Time to Transfusion Independence	Transfusion independence was defined as the absence of an intravenous infusion of any RBC transfusion during any consecutive "rolling" 56 days during the treatment period (e.g., Days 1 to 56, Days 2 to 57, Days 3 to 58, etc.), and accompanied by at least a 1 g/dL increase from screening/baseline in hemoglobin. Time to transfusion independence was defined as the day of the first dose of study drug to the first day of the first 56-day RBC transfusion-free period.	up to 2 years
Secondary	Participants Who Relapsed or Maintained Their Transfusion Independence After Achieving Transfusion Independence During the Study	Transfusion independence was defined as the absence of an intravenous infusion of any RBC transfusion during any consecutive "rolling" 56 days during the treatment period (e.g., Days 1 to 56, Days 2 to 57, Days 3 to 58, etc.), and accompanied by at least a 1 g/dL increase from screening/baseline in hemoglobin. Participants who relapsed required a transfusion after the period of transfusion independence. Participants who maintained transfusion independence did not require a transfusion during the remainder of the study.	up to 2 years
Secondary	Kaplan Meier Estimate for Duration of Transfusion Independence Response	Duration of response is measured from the first of the consecutive 56 days during which the participant was free of RBC transfusions to the date of the first RBC transfusion after this period. Duration of response was censored at the date of last visit for participants who maintained transfusion independence.	up to 2 years
Secondary	Change in Hemoglobin Concentration From Baseline to Maximum Value During Response Period for Responders	The change from baseline in hemoglobin for participants who became RBC-transfusion independent. The maximum hemoglobin value obtained during the response period is used in the calculation of change from baseline.	Baseline (Day -54 to Day 0), During study (Day 1 up to 2 years)
Secondary	Participant Counts of Cytogenetic Response	Participants deemed evaluable by the central cytogenetic review had their cytogenetic response categorized as major or minor. A major cytogenetic response was defined as = 20 metaphases recorded at baseline, and at least; 1 post baseline evaluation with = 20 metaphases analyzed with no abnormal metaphases observed. A minor cytogenetic response was defined as = 20 metaphases analyzed at baseline, and at least 1 post baseline evaluation with = 20 metaphases analyzed with a = 50% reduction in the proportion of hematopoietic cells with cytogenetic abnormalities compared with baseline.	up to 2 years
Secondary	Participant Counts of Platelet Response	Major platelet response: participants with a minimum pretreatment platelet of <100,000/mm^3 in all values within 56 days of start of treatment, an absolute increase of =30,000/mm^3 sustained for =56 consecutive days. In platelet transfusion-dependent participants, a major response was stabilization of platelet counts and platelet transfusion independence.; Minor platelet response: participants with a minimum pretreatment platelet of <100,000/mm^3, a = 50% increase in platelet count with a net increase >10,000/mm^3 for a consecutive 56-day period in the absence of platelet transfusions.	up to 2 years
Secondary	Participant Counts of Absolute Neutrophil Count (ANC) Response	Major neutrophil response: participants with a minimum pretreatment ANC concentration of < 1500/mm^3 in all values obtained within 56 days of start of treatment, a = 100% increase or an absolute increase of; = 500/mm^3, whichever was greater (at least to be = 500/mm^3), sustained for 56 consecutive days. Minor neutrophil response: participants with a minimum pretreatment ANC concentration of < 1500/mm^3, an increase in ANC concentration of = 100% sustained for 56 consecutive days.	up to 2 years
Secondary	Participants With Complete or Partial Bone Marrow Improvement	Bone marrow aspirates were assessed by a central reviewer. A complete bone marrow improvement required a baseline French-American-British (FAB) classification (see Baseline Characteristics) of refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), refractory anemia with excess blasts (RAEB) or chronic myelomonocytic leukemia (CMML) and a during study assessment of no MDS. A partial bone marrow improvement reflected an improved FAB classification compared to baseline (e.g. RARS to RA) but evidence of MDS continued to exist.	up to 2 years
Secondary	Participants With Bone Marrow Progression	Bone marrow aspirate was assessed by a central reviewer. Progression is represented in two categories according to changes from baseline in French-American-British (FAB) classification (see Baseline Characteristics): Baseline classification of refractory anemia (RA) or refractory anemia with ringed sideroblasts (RARS) to a during treatment (plus 30 days) classification of refractory anemia with excess blasts (RAEB).; Any baseline FAB classification to a during treatment (plus 30 days) classification of acute myeloid leukemia (AML).	up to 2 years