A Safety Study of Rituximab Plus MTX Injected Into the Cerebrospinal Fluid in the Treatment of Brain Lymphoma
Phase I Study of Intraventricular Administration of Rituximab in Combination With Methotrexate in the Treatment of Recurrent CNS and Intraocular Lymphoma
2 other identifiers
interventional
14
1 country
4
Brief Summary
Rituximab is the first monoclonal antibody to receive approval in the treatment of cancer and has been proven to lead to extended survival when administered intravenously in the treatment of patients with systemic non-Hodgkin's lymphoma. We have previously demonstrated that a small fraction of Rituximab administered intravenously is able to cross the blood-brain-barrier into the brain. We will test the idea that the direct injection into the cerebrospinal fluid of Rituximab, a monoclonal antibody which attacks and kills lymphoma cells, is safe and when used in combination with methotrexate in patients with recurrent brain and intraocular lymphoma. We will also test the idea that the combination of rituximab plus methotrexate has activity and is effective in the treatment of recurrent brain and intraocular lymphoma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Apr 2007
Longer than P75 for phase_1
4 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 14, 2005
CompletedFirst Posted
Study publicly available on registry
September 22, 2005
CompletedStudy Start
First participant enrolled
April 1, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2013
CompletedFebruary 16, 2015
February 1, 2015
4.8 years
September 14, 2005
February 12, 2015
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
whether intra-CSF administration of rituximab in combination with MTX in patients with recurrent CNS and intraocular lymphoma is associated with neurotoxicity
4 weeks
Secondary Outcomes (1)
To define the rate of tumor response (CR plus PR) in the brain, spine, eye, or CSF.
4 weeks
Study Arms (1)
Rituximab Plus MTX
EXPERIMENTALInterventions
Intraventricular injection of rituximab into an Ommaya reservoir on day 1 of each week. Intraventricular rituximab plus methotrexate (MTX) on day 4 of each week. First three patients at dose A : 25 mg rituximab on day 1, and MTX (12 mg) plus rituximab (10 mg) on day 4 each week. If there are no dose limiting toxicities at Dose A in all of the first 3 patients or in 5 of the first 6 patients, the next 3 patients will receive dose level B: 25 mg rituximab on day 1, and combination MTX (12 mg) plus rituximab (25 mg) on day 4 of each week. Oral leucovorin rescue 24 hours after each MTX administration. Maximum injections will be 16 over 9-weeks. Subjects who experience a partial response at week 10 will be given the option for extended dosing.
Eligibility Criteria
You may qualify if:
- Relapsed, refractory CNS lymphoma, ocular lymphoma, lymphomatous meningitis
- Tumors must be CD20 + on pathologic analysis.
- Patients must have an Ommaya reservoir (ventricular access device.
- Patients may have had prior intrathecal methotrexate, ara-C or thiotepa but must have recovered from any reversible toxicity caused by prior treatment.
- Concurrent systemic chemotherapy is allowed for treatment of disease outside the meninges with the exception of high-dose methotrexate (\>500 mg/m2/d, high-dose ara-C (\> 2 gm/m2/d), high-dose thiotepa (\>300 mg/m2/d) or investigational agents.
- Patients must have sufficient baseline hematologic function: \>1,500 granulocytes and \>50,000 platelets/ul.
- Patients must have had a nuclear medicine CSF flow study performed within 30 days of treatment which shows no significant obstruction within the ventricles.
You may not qualify if:
- History of whole brain or craniospinal irradiation or intrathecal chemotherapy \< 4 days before initiation of intra-CSF administration of rituximab.
- Anticipated survival of less than one month.
- HIV infection. -
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (4)
University of California, San Francisco
San Francisco, California, 94143, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, 94123, United States
MD Anderson Cancer Center
Houston, Texas, United States
Related Publications (1)
Rubenstein JL, Li J, Chen L, Advani R, Drappatz J, Gerstner E, Batchelor T, Krouwer H, Hwang J, Auerback G, Kadoch C, Lowell C, Munster P, Cha S, Shuman MA, Damon LE. Multicenter phase 1 trial of intraventricular immunochemotherapy in recurrent CNS lymphoma. Blood. 2013 Jan 31;121(5):745-51. doi: 10.1182/blood-2012-07-440974. Epub 2012 Nov 29.
PMID: 23197589DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
James L. Rubenstein, MD PhD
University of California, San Francisco
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 14, 2005
First Posted
September 22, 2005
Study Start
April 1, 2007
Primary Completion
January 1, 2012
Study Completion
March 1, 2013
Last Updated
February 16, 2015
Record last verified: 2015-02