Clinical Trial: Lenalidomide Plus Rituximab for Recurrent/Refractory CNS and Intraocular Lymphoma

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Lenalidomide Plus Rituximab for Recurrent/Refractory CNS and Intraocular Lymphoma

Brief Summary: 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®).

Detailed Summary:

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.


Sponsor: University of California, San Francisco

Current Primary Outcome: 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. ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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. ]
  • 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. ]
  • 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. ]
  • 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. ]
    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. ]


Original Secondary Outcome:

  • 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. ]
  • 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. ]
  • To define the effects of lenalidomide on CSF cytokine profiles (Th1 vs. Th2), macrophage phenotypes, T-cell subsets, natural killer cell infiltration using flow-cytometry of 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. ]
  • 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. ]
    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. ]


Information By: University of California, San Francisco

Dates:
Date Received: February 27, 2012
Date Started: December 2012
Date Completion: June 2017
Last Updated: January 14, 2015
Last Verified: January 2015