Lenalidomide + Plerixafor in Previously Treated Chronic Lymphocytic Leukemia (CLL)
In research studies, lenalidomide (also called Revlimid) has shown some response in chronic lymphocytic leukemia (CLL); however, responses are usually partial responses that occur after several months of taking the study drug. It is thought that by adding the drug plerixafor (also called Mozobil) responses may be improved and/or occur sooner.
The main purpose of this study is to determine the dose of plerixafor that is safe to use in combination with lenalidomide. The study will also look at the response rates of the combination of lenalidomide and plerixafor and the effect the study drugs have on CLL cells.
Leukemia, Lymphocytic, Chronic, B-Cell
Drug: Lenalidomide + Plerixafor (+ Rituximab)
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Lenalidomide in Combination With Plerixafor in Patients With Previously Treated Chronic Lymphocytic Leukemia|
- Maximum Tolerated Dose [ Time Frame: 4-16 months ] [ Designated as safety issue: Yes ]
- Response (CR/PR) [ Time Frame: at the end of 4 months of combination treatment and at 2 months after completion of therapy ] [ Designated as safety issue: No ]
- Progression-free survival (PFS) [ Time Frame: time from day 1 of treatment to disease progression, death, or 2 years, whichever comes first ] [ Designated as safety issue: No ]
- Overall survival (OS) [ Time Frame: the time from day 1 of treatment to death or 2 years, whichever comes first ] [ Designated as safety issue: No ]
- Reduction in severity of B symptoms [ Time Frame: at the end of stage 1 (lenalidomide alone), at the end of stage 2 (4 months of combination), and at 2 months post-completion of therapy ] [ Designated as safety issue: No ]Reduction in the severity of the following B symptoms will be assessed: fever ≥ 101F, chills, night sweats, and anorexia with weight loss.
- Reduction in the frequency of blood and platelet transfusions [ Time Frame: 4 weeks prior to therapy and in the 4 weeks following the completion of therapy ] [ Designated as safety issue: No ]The change in number of transfusions from pre- to post-treatment will be calculated and summarized across all patients by giving the minimum, the 25th, 50th (median) and the 75th percentile and the maximum.
- Reduction in the number of B-symptoms [ Time Frame: at the end of stage 1 (lenalidomide alone), at the end of stage 2 (4 months of combination), and at 2 months post-completion of therapy ] [ Designated as safety issue: No ]
|Study Start Date:||January 2012|
|Estimated Study Completion Date:||June 2016|
|Estimated Primary Completion Date:||June 2014 (Final data collection date for primary outcome measure)|
Experimental: Lenalidomide + Plerixafor+ Rituximab
Drug: Lenalidomide + Plerixafor (+ Rituximab)
The combination of lenalidomide and plerixafor will be evaluated in this single institution, open label clinical study of subjects with relapsed chronic lymphocytic leukemia (CLL). The overall design of the phase 1 study includes up to three treatment "stages."
Each subject will receive lenalidomide 5mg by mouth daily beginning on cycle 1 day 1. If tolerated, the dose will be increased by 2.5mg every 7 days to a maximum dose of 10mg by mouth daily (Stage 1). Once the subject is stably maintained on a daily dose of lenalidomide of 10mg daily and the white blood cell (WBC) count is <100.0 x 109 / L, and has been taking lenalidomide for at least 28 days, plerixafor will be added (Stage 2). In the dose escalation phase, 4 different doses of plerixafor in combination with lenalidomide will be studied in cohorts of 3 to 6 subjects each, following a standard "3 + 3" format:
- Cohort 1: plerixafor 0.24 mg/kg subcutaneous (SC) daily thrice weekly (Mon, Wed, Fri)
- Cohort 2: plerixafor 0.32 mg/kg SC daily thrice weekly (Mon, Wed, Fri)
- Cohort 3: plerixafor 0.42 mg/kg SC daily thrice weekly (Mon, Wed, Fri)
- Cohort 4: plerixafor 0.54 mg/kg SC daily thrice weekly (Mon, Wed, Fri) Plerixafor will be administered for 3 weeks of each cycle (days 1, 3, 5, 8, 10, 12, 15, 17, and 19) followed by a 1 week rest period. Lenalidomide dosing will be continuous.
An interim assessment of response will be performed after 4 cycles of combination therapy:
- Subjects achieving a complete response (CR) by National Cancer Institute (NCI)-96 criteria will continue lenalidomide monotherapy (plerixafor is discontinued) until disease progression.
- Subjects achieving a partial response (PR) will continue both lenalidomide and plerixafor. Additionally, rituximab 375mg/m2 will be added on day 1 of each subsequent cycle beginning with cycle 5, day 1 of combination therapy. (Stage 3). Treatment with the combination of lenalidomide and plerixafor will continue for a maximum of 12 cycles of combination therapy. Subjects may receive up to 8 doses of rituximab concurrent with lenalidomide and plerixafor on day 1 of each cycle. Subjects will then continue single agent lenalidomide until disease progression.
- Subjects with stable disease may continue lenalidomide and plerixafor at the discretion of the investigator and the subject. Rituximab 375 mg/m2 will be added on day 1 of each subsequent cycle. Treatment, dose, schedule, and duration are the same as for subjects achieving a PR.
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|Study Director:||Mark Lanasa, MD, PhD||Unafilliated|
|Principal Investigator:||David A Rizzieri, MD||Duke University|