A Phase 2, Multi-Center, Randomized, Double-Blinded, Parallel Group Study of the Safety and Efficacy of Different Lenalidomide (REVLIMID®) Dose Regimens in Subjects With Relapsed or Refractory B-Cell Chronic Lymphocytic Leukemia
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Celgene
- Enrollment
- 104
- Locations
- 52
- Primary Endpoint
- Number of Participants With Treatment-emergent Adverse Events
Study Overview
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).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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.
Exclusion Criteria
- •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
Arms & Interventions
Lenalidomide 5 mg
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
Intervention: lenalidomide (Drug)
Lenalidomide 10 mg
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
Intervention: lenalidomide (Drug)
Lenalidomide 15 mg
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
Intervention: lenalidomide (Drug)
Outcomes
Primary Outcomes
Number of Participants With Treatment-emergent Adverse Events
Time Frame: 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 Outcomes
- Kaplan-Meier Estimate of Event-Free Survival(From randomization until the end of the study; maximum time on study was 91 months.)
- 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.)
- 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.)
- Kaplan-Meier Estimate of Time to Progression(From randomization until the end of the study; maximum time on study was 91 months.)
- Kaplan-Meier Estimate of Progression Free Survival(From randomization until the end of the study; maximum time on study was 91 months.)
- Kaplan-Meier Estimate of Overall Survival(From randomization until the end of the study; maximum time on study was 91 months.)
- 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.)