Lenalidomide Plus Rituximab for Recurrent/Refractory CNS and Intraocular Lymphoma
Rationale for the Proposed Study
There is evidence that immunomodulatory drugs such as lenalidomide stimulate immune
effectors such as natural killer (NK) cells, and thus promote rituximab efficacy via ADCC.
Because of the evidence for synergy between rituximab and lenalidomide in NHL, patients who
do not respond to lenalidomide monotherapy will receive combined intravenous plus
intraventricular rituximab in addition to lenalidomide. To maximize delivery to the central
nervous system (CNS), the investigators propose to administer rituximab via both intravenous
and intraventricular routes. The rationale for intraventricular administration of rituximab
is the demonstration that approximately 0.1% of systemically administered rituximab
penetrates the cerebral spinal fluid (CSF) but that intraventricular administration of
rituximab is both feasible and achieves high concentrations that are associated with
anti-lymphoma activity. This study will thus build upon the two Phase 1 trials of
intraventricular rituximab that have been conducted at UCSF to define the safety of the
intraventricular route of administration; this study will, however, be the first to evaluate
the combination of intraventricular plus intravenous treatment.
The rationale for intravenous administration of rituximab in recurrent CNS lymphoma is that
the blood-brain-barrier is likely partially disrupted, particularly when there is
lymphoma-associated contrast enhancement detectable on the MRI, and the fact that there is
evidence for activity when rituximab is administered intravenously, both as monotherapy
(Batchelor et al., 2011) and potentially in combination with chemotherapy.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To establish the maximal tolerated dose (MTD) of Lenalidomide in patients with recurrent CNS NHL and intraocular NHL
Participants will be followed for the duration of treatement, an expected average of 4 months.
James Rubenstein, MD, PhD
University of California, San Francisco
United States: Food and Drug Administration
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