Phase II Clinical Protocol for the Treatment of Patients With Previously Untreated CLL With Four or Six Cycles of Fludarabine and Cyclophosphamide With Rituximab (FCR) Plus Lenalidomide Followed by Lenalidomide Consolidation/ Maintenance
The primary objective is to evaluate the complete response rate following 4 cycles of
FCR-Lite plus lenalidomide in previously untreated patients with CLL.
The first secondary objective is to evaluate the toxicity of patients with previously
untreated CLL treated with FCR-Lite plus lenalidomide, followed by lenalidomide. The second
is to evaluate the overall response rate and overall survival of patients with previously
untreated CLL treated with FCR-Lite plus lenalidomide followed by lenalidomide. The third
is to determine whether adding lenalidomide as a consolidation/maintenance therapy will
eliminate bone marrow minimal residual disease in CR patients and whether patients who have
a PR after 6 cycles of FCR-Lite plus lenalidomide will respond to 12 months of lenalidomide.
The final secondary objective is to determine whether the expression of ZAP-70, CD38, and
chromosomes correlate with response rate, duration of response, and survival for previously
untreated patients with CLL.
2-stage phase 2 study-design. 19 subjects are treated in stage-1 with FCR-Lite plus 5mg
lenalidomide increasing to 10mg and 15mg in subsequent cycles depending on toxicity. If
there are at least 5 CRs the study will accrue an additional 35 subjects (see statistical
section). A secondary objective of this study will be to determine if MRD positive patients
will become MRD negative with lenalidomide consolidation/maintenance and whether PR
patients will convert to CRs Lenalidomide will begin 2 months after the last dose of
FCR-Lite in all subjects with CR. It may begin as soon as 1 month after FCR-Lite plus
lenalidomide in subjects with PR. Lenalidomide is given in 28 d cycles increasing the dose
from 5 mg/d to 10 mg/d in cycle 2 and to 15mg in cycles 3-6 if well- tolerated (no grade-3
or -4 toxicity). Patients with creatinine clearance ≥30ml/min and <60ml/min will start at
2.5mg daily increasing to 5 and 10mg in subsequent cycles . Reduction to the prior dose is
allowed for grade-3/-4 toxicity. MRD will be studied by flow cytometry from bone marrow
and peripheral blood samples following 4 and 6 cycles of FCR-Lite and after 6 and 12 months
of lenalidomide in CR patients.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Analysis of the Primary Endpoint: The complete responses will be estimated by the number of patients with CR divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the true CR will be calculated
Anthony Mato, MD
John Theurer Cancer Center at HackensackUMC
United States: Food and Drug Administration
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