Study of Lenalidomide to Evaluate Safety and Efficacy in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia
- Conditions
- Relapsed or Refractory Chronic Lymphocytic Leukemia
- Interventions
- Registration Number
- NCT00963105
- Lead Sponsor
- Celgene
- Brief Summary
The purpose of this study is to determine the safety and effectiveness of different dose regimens of lenalidomide in patients with relapsed or refractory chronic lymphocytic leukemia (CLL).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 104
- 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
- Must have a documented diagnosis of B-cell CLL
- Must be relapsed or refractory to at least 1 regimen for treatment of CLL. At least one of the prior treatments must have included a purine analog-based or bendamustine-based regimen
- Must have an Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2.
- Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form
- Active infections requiring systemic antibiotics
- Systemic treatment for B-cell CLL within 28 days of initiation of lenalidomide treatment
- Alemtuzumab therapy within 120 days of initiating lenalidomide treatment
- Prior therapy with lenalidomide
- History of grade 4 rash due to prior thalidomide treatment
- Planned autologous or allogeneic bone marrow transplantation
- Central nervous system (CNS) involvement as documented by spinal fluid cytology or imaging.
- Uncontrolled hyperthyroidism or hypothyroidism
- Venous thromboembolism within 12 months
- ≥ Grade 2 neuropathy
- Uncontrolled autoimmune hemolytic anemia or thrombocytopenia
- Disease transformation [i.e. Richter's Syndrome (lymphomas) or prolymphocytic leukemia]
- Participation in any clinical study or having taken any investigational therapy within 28 days prior to initiating lenalidomide therapy
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Lenalidomide 10 mg lenalidomide Participants received a starting dose of 10 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability. Participants continued receiving study drug until disease progression or unacceptable toxicity, unless they withdrew consent or had other reasons to discontinue from study drug Lenalidomide 15 mg lenalidomide Participants received a starting dose of 15 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability. Participants continued receiving study drug until disease progression or unacceptable toxicity, unless they withdrew consent or had other reasons to discontinue from study drug Lenalidomide 5 mg lenalidomide Participants received a starting dose of 5 mg lenalidomide orally once a day. Lenalidomide dose was escalated by 5 mg in a step-wise manner every 28 days up to a maximum dose of 25 mg daily based on tolerability. Participants continued receiving study drug until disease progression or unacceptable toxicity, unless they withdrew consent or had other reasons to discontinue from study drug
- Primary Outcome Measures
Name Time Method Number of Participants With Treatment-emergent Adverse Events From first dose of study drug to 30 days after the last dose; the maximum duration of treatment was 251, 265, and 267 weeks in the 5 mg, 10 mg, and 15 mg treatment groups respectively. Adverse events (AEs) were graded for severity by the investigator according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 with the exceptions of hematologic toxicities and tumor lysis syndrome, according to the following scale: Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life Threatening or disabling AE Grade 5 = Death The investigator determined the relationship of each AE to study drug based on the timing of the AE and whether other medications, therapeutic interventions, or underlying conditions could provide a sufficient explanation for the observed event.
- Secondary Outcome Measures
Name Time Method Overall Response Rate (ORR) Response was assessed after 3 cycles of therapy (Week 12) and every 4 weeks thereafter until disease progression. Maximum time on study was 91 months. ORR was defined as the percentage of patients with a complete response (CR), CR with incomplete bone marrow (BM) recovery (CRi) or partial response (PR) during treatment. Response was assessed according to the 2008 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines. Per the guidelines, a CR required peripheral blood lymphocytes below 4 x 10\^9/L, absence of lymphadenopathy, no hepatomegaly or splenomegaly, absence of disease and blood counts neutrophils \>1.5 x 10\^9/L, platelets \>100 x 10\^9/L, hemoglobin (hgb) \>11g/dL) and BM at least normocellular for age. CRi = CR with incomplete BM recovery. PR = required at least 2 months from end of treatment, a ≥50% decrease in peripheral blood lymphocyte count from the pre-treatment value and either a ≥ 50% reduction in lymphadenopathy or ≥50% reduction of liver enlargement or ≥50% reduction of spleen enlargement plus neutrophils \>1.5 x 10\^9/ or ≥50% increase, platelets \>100 x 10\^9/L or ≥50% increase, hgb 11 g/dL.
Kaplan-Meier Estimate of Duration of Response Response was assessed after 3 cycles of therapy (Week 12) and every 4 weeks thereafter until disease progression. Maximum time on study was 91 months. Duration of response (DOR) was defined as the time from the first visit where PR, CRi, or CR was documented to progressive disease (PD). Duration of response was censored at the last date that the participant was known to be progression-free for participants who had not progressed at the time of analysis or who withdrew consent or were lost to follow-up prior to documentation of progression.
Kaplan-Meier Estimate of Time to Progression From randomization until the end of the study; maximum time on study was 91 months. Time to progression (TTP) was defined as the time from randomization to the first documented progression. For participants who did not progress during the study, TTP was censored at the last adequate response assessment showing evidence of no disease progression.
Kaplan-Meier Estimate of Event-Free Survival From randomization until the end of the study; maximum time on study was 91 months. Event-free survival (EFS) is the interval between the start of treatment to the first sign of disease progression, or treatment for relapse or death (whichever occurred first). If withdrawal of consent or loss to follow-up occurred before documented progression or death, then these observations were censored at the date when the last complete tumor assessments determined a lack of progression.
Kaplan-Meier Estimate of Progression Free Survival From randomization until the end of the study; maximum time on study was 91 months. Progression-free survival (PFS) was calculated as the time from randomization to the first documented progression or death due to any cause during or after the treatment period, whichever occurred first. The progression date was assigned to the earliest time when any progression is observed without prior missing assessments. If withdrawal of consent or loss to follow-up occurred before documented progression or death, then these observations were censored at the date when the last complete tumor assessments determined a lack of progression.
Kaplan-Meier Estimate of Overall Survival From randomization until the end of the study; maximum time on study was 91 months. Overall survival (OS) was defined as the time from randomization to death from any cause. Overall survival was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who had withdrawn consent or were lost to follow-up before death was documented.
Time to Response Response was assessed after 3 cycles of therapy (Week 12) and every 4 weeks thereafter until disease progression. Maximum time on study was 91 months. Time to response (TTR) was calculated as the time from randomization to the first documented date of response (PR, CRi or CR) based on iwCLL guidelines for participants with an objective response during the treatment period.
Trial Locations
- Locations (52)
Desert Hematology Oncology Medical Group, Inc.
🇺🇸Rancho Mirage, California, United States
Cancer Center of Central Connecticut
🇺🇸Southington, Connecticut, United States
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
CHU Sud
🇫🇷Amiens, France
Hopital Pitie Salpetriere
🇫🇷Paris, France
I.R.C.C.S. Ospedale San Raffaele
🇮🇹Milano, Italy
Universita' Degli Studi Di Perugia
🇮🇹Perugia, Italy
UCSD Moores Cancer Center
🇺🇸La Jolla, California, United States
Stanford University School of Medicine
🇺🇸Stanford, California, United States
Cancer and Blood Disease Center
🇺🇸Lecanto, Florida, United States
Northwestern University Medical Center Division of Hematology Oncology
🇺🇸Chicago, Illinois, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Indiana University Cancer Center
🇺🇸Indianapolis, Indiana, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Long Island Jewish Medical Center CLL Research and Treatment Program
🇺🇸New Hyde Park, New York, United States
Gabrail Cancer Center Research
🇺🇸Canton, Ohio, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Wake Forest University School of Medicine
🇺🇸Winston-Salem, North Carolina, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Drexel University, College of Medicine, Clinical Research Group
🇺🇸Philadelphia, Pennsylvania, United States
CHU Montpellier - Hôpital Saint Eloi
🇫🇷Montpellier Cedex 5, France
Hopital Emile Muller
🇫🇷Mulhouse, France
Juravinski Cancer Centre
🇨🇦Hamilton, Ontario, Canada
Hopital Avicenne
🇫🇷Bobigny Cedex, France
CHU Grenoble
🇫🇷Grenoble Cedex 09, France
Clinique Victor Hugo
🇫🇷Le Mans, France
Institut Paoli Calmettes
🇫🇷Marseille Cedex 9, France
CHRU - Hopital du Haut Leveque
🇫🇷Pessac, France
CH Perpignan - Hopital Saint-Jean
🇫🇷Perpignan, France
Hopital Robert Debre
🇫🇷REIMS cedex, France
CHU Rennes Hematology
🇫🇷Rennes cedex, France
Centre Hospitalier Lyon Sud
🇫🇷Pierre Bénite, France
CHRU Hopital Brabois
🇫🇷Vandoeuvre les Nancy, France
Universitatsklinikum Essen
🇩🇪Essen, Germany
Universitatsklinikum Schleswig Holstein
🇩🇪Kiel, Germany
Charite -Universitätsmedizin Berlin
🇩🇪Berlin, Germany
Azienda Ospedaliera Universitaria San Martino
🇮🇹Genova, Italy
University of Ulm Abteilung Innere Medizin III
🇩🇪Ulm, Germany
Klinikum der Universitat zu Koln
🇩🇪Köln, Germany
Ernst-Moritz-Arndt-Universität Greifswald
🇩🇪Greifswald, Germany
Ematologia ed Immunologia, Azienda Ospedaliera "Vito Fazzi" di Lecce
🇮🇹Lecce, Italy
Istituto Europeo di Oncologia - IEO
🇮🇹Milano, Italy
Universita degli Studi di Padova
🇮🇹Padova, Italy
Hospital Universitari Germans Trias i Pujol
🇪🇸Barcelona, Spain
Hospital Clinic Provincial de Barcelona
🇪🇸Barcelona, Spain
Karolinska Universitetssjukhuset
🇸🇪Stockholm, Sweden
St James's Institute of Oncology
🇬🇧Leeds, United Kingdom
The Royal Marsden Hospital
🇬🇧London, United Kingdom
St.Bartholomew's Hospital
🇬🇧London, United Kingdom
King's College Hospital
🇬🇧London, United Kingdom
Christie Hospital NHS Foundation Trust
🇬🇧Manchester, United Kingdom