Lenalidomide Plus Rituximab for Recurrent/Refractory CNS and Intraocular Lymphoma
This is a Phase I study, which means that the goal is to see if the study treatment is safe. The purpose of this study is to test the safety of Lenalidomide at different dose levels, and to test the safety of Lenalidomide alone or in combination with Rituximab (also known as Rituxan®).
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Lenalidomide Plus Rituximab for Recurrent/Refractory CNS and Intraocular Lymphoma|
- To establish the maximal tolerated dose (MTD) of Lenalidomide in patients with recurrent CNS NHL and intraocular NHL [ Time Frame: Participants will be followed for the duration of treatement, an expected average of 4 months. ] [ Designated as safety issue: Yes ]
- To define the extent of cerebrospinal fluid (CSF) penetration of lenalidomide. [ Time Frame: Participants will have CSF withdrawn every 4 weeks while on treatment. Average study participation is approximately 4 months. ] [ Designated as safety issue: No ]
- To assess the clinical efficacy Lenalidomide monotherapy as measured by cytologic, neurologic, radiographic, and ocular (for patients with intraocular lymphoma) response criteria. [ Time Frame: Participants will have weekly evaluations at clinic visits for the duration of treatment. Average study participation is approximately 4 months. ] [ Designated as safety issue: No ]
- To define the immunological effects of lenalidomide using flow-cytometry CSF as well as genomic markers of recurrent/refractory CNS lymphoma. [ Time Frame: Participants will have CSF withdrawn every 4 weeks while on treatment. Average study participation is approximately 4 months. ] [ Designated as safety issue: No ]
- To assess the clinical efficacy of combined intraventricular plus systemic rituximab administration in combination with lenalidomide as measured by cytologic, neurologic, and radiographic response criteria. [ Time Frame: Participants will have weekly evaluations at clinic visits for the duration of treatment. Average study participation is approximately 4 months. ] [ Designated as safety issue: No ]Objective only applies to patients with recurrent CNS lymphoma not responding to lenalidomide as monotherapy
- To determine a potential impact of intravenous rituximab administration on the rate of rituximab clearance from the CSF after intraventricular rituximab administration. [ Time Frame: Participants will have CSF withdrawn every 4 weeks while on treatment. Average study participation is approximately 4 months. ] [ Designated as safety issue: No ]
|Study Start Date:||December 2012|
|Estimated Study Completion Date:||June 2017|
|Estimated Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
Formulation of Dosage forms: 5 mg, 10 mg, 15 mg and 25 mg capsules.
Dosage: 10 mg - 30 mg (Treatment 1 and Treatment 2)
Route of administration: Oral
Formulation of Dosage forms: 100 mg/IO mL and 500 mg/50 mL solution in a single-use vial
Dosage: 375 mg/m2, intravenous (Treatment 2, Cycle 1 only); 25 mg intraventricular injection (Treatment 2, all cycles)
Route of administration: Intravenous (Treatment 2, Cycle 1 only); Intraventricular injection (Treatment 2, all cycles)
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01542918
|Contact: James Rubenstein, MD, PhDfirstname.lastname@example.org|
|United States, California|
|University of California, San Francisco||Recruiting|
|San Francisco, California, United States, 94143|
|Contact: Paula Fiermonte 415-885-7605 FiermonteP@cc.ucsf.edu|
|Principal Investigator: James Rubenstein, MD, PhD|
|Principal Investigator:||James Rubenstein, MD, PhD||University of California, San Francisco|