A Safety Study of Rituximab Plus MTX Injected Into the Cerebrospinal Fluid in the Treatment of Brain Lymphoma

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2012 by University of California, San Francisco.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00221325
First received: September 14, 2005
Last updated: October 10, 2012
Last verified: October 2012

September 14, 2005
October 10, 2012
April 2007
January 2012   (final data collection date for primary outcome measure)
whether intra-CSF administration of rituximab in combination with MTX in patients with recurrent CNS and intraocular lymphoma is associated with neurotoxicity [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
Not Provided
Complete list of historical versions of study NCT00221325 on ClinicalTrials.gov Archive Site
To define the rate of tumor response (CR plus PR) in the brain, spine, eye, or CSF. [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
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

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.

Rituximab is the first monoclonal antibody to receive FDA approval in the treatment of cancer. Intravenous administration of rituximab has been demonstrated to lead to prolongation of survival when used in combination with chemotherapy 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 and we have also previously demonstrated that direct intraventricular administration of Rituximab is able to achieve high concentrations within the cerebrospinal fluid ventricles and lumbar sac.

We will test the hypothesis that the direct intraventricular injection of Rituximab in combination with Methotrexate is safe and when used in combination in patients with recurrent brain and intraocular lymphoma. We will evaluate the safety of this combination by testing different dose levels of Rituximab. We will also measure the concentration of Rituximab in the intraocular compartments and cerebrospinal fluid at different time points after intraventricular administration to determine the pharmacokinetics of intrathecal Rituximab as well as the potential impact of Methotrexate on Rituximab distribution.

We will also test the hypothesis that the intraventricular administration of the combination of rituximab plus methotrexate has activity and is effective in the treatment of recurrent brain and intraocular lymphoma.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Central Nervous System Lymphoma
  • Intraocular Lymphoma
Drug: Intraventricular Rituximab Plus MTX

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.

Other Names:
  • MTX
  • amethopterin
  • Rituxan
  • MabThera
Experimental: Rituximab Plus MTX
Intervention: Drug: Intraventricular Rituximab Plus MTX
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
20
April 2013
January 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Relapsed, refractory CNS lymphoma, ocular lymphoma, lymphomatous meningitis
  2. Tumors must be CD20 + on pathologic analysis.
  3. Patients must have an Ommaya reservoir (ventricular access device.
  4. Patients may have had prior intrathecal methotrexate, ara-C or thiotepa but must have recovered from any reversible toxicity caused by prior treatment.
  5. 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.
  6. Patients must have sufficient baseline hematologic function: >1,500 granulocytes and >50,000 platelets/ul.
  7. Patients must have had a nuclear medicine CSF flow study performed within 30 days of treatment which shows no significant obstruction within the ventricles.

Exclusion Criteria:

  1. History of whole brain or craniospinal irradiation or intrathecal chemotherapy < 4 days before initiation of intra-CSF administration of rituximab.
  2. Anticipated survival of less than one month.
  3. HIV infection. -
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00221325
CC05254, H9414-29670
Yes
University of California, San Francisco
University of California, San Francisco
Not Provided
Study Chair: James L. Rubenstein, MD PhD University of California, San Francisco
University of California, San Francisco
October 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP