Methotrexate, Mannitol, Rituximab, and Carboplatin in Treating Patients With Newly Diagnosed Primary Central Nervous System Lymphoma

Conditions:Brain Cancer, Lymphoma
Therapuetic Areas:Oncology
Age Range:18 - 75
Start Date:October 2005
End Date:January 2020

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A Phase I/II Study of Patients With Newly Diagnosed Primary Central Nervous System Lymphoma Treated With Methotrexate/BBBD, and Adding Rituximab (an Anti CD-20 Antibody) and Carboplatin, to the Treatment Regimen

This phase I/II trial studies the side effects of methotrexate, mannitol, rituximab, and
carboplatin and to see how well they work in treating patients with primary central nervous
system lymphoma. Drugs used in chemotherapy, such as methotrexate and carboplatin, work in
different ways to stop the growth of cancer cells, either by killing the cells, by stopping
them from dividing, or by stopping them from spreading. Osmotic blood-brain barrier
disruption uses mannitol to open the blood vessels around the brain and allow cancer-killing
substances to be carried directly to the brain. Monoclonal antibodies, such as rituximab, may
block cancer growth in different ways by targeting certain cells. Giving methotrexate,
mannitol, rituximab, and carboplatin together may be an effective treatment for primary
central nervous system lymphoma.


I. To evaluate the safety and toxicities of a treatment regimen consisting of rituximab
(intravenously [IV]) the day prior to methotrexate (intra-arterially [IA]), and carboplatin
(IA) in conjunction with blood-brain barrier disruption (BBBD) and delayed sodium thiosulfate

II. To demonstrate, adding a monoclonal antibody and carboplatin to methotrexate BBBD, that a
45% rate of complete response (CR) within the first 3 months of treatment is achieved, while
excluding a CR rate as low as 30%.


I. To estimate the response rate (counting all CRs), the two-year overall survival and the
two-year event-free survival, as baselines for subsequent trials.


Patients receive rituximab IV over 5 hours on day 1, mannitol IA, methotrexate IA over 10
minutes, and carboplatin IA over 10 minutes on days 2 and 3. Patients then receive sodium
thiosulfate IV over 15 minutes at 4 and 8 hours after carboplatin. Treatment repeats monthly
for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 2 months, then every 2
months for 2 years, every 6 months for 1 year, and then annually for at least 2 years.

Inclusion Criteria:

- Subjects with histopathologic confirmation of intermediate or high-grade primary
central nervous system lymphoma (PCNSL) as documented by brain biopsy, or cytology
(analysis from cerebral spinal fluid [CSF] or vitrectomy), and cluster of
differentiation 20 (CD20) positive; whenever possible, the tumor should be
characterized by immunophenotype

- Subjects must be =< 90 days from diagnosis of PCNSL in the brain or spine; time from
pathologic diagnosis to initiation of treatment should be specified; subjects with
history of only ocular lymphoma are eligible if < 90 days since documented brain
parenchymal disease (by imaging or by biopsy)

- Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance score =< 3
(Karnofsky >= 30)

- Hematocrit >= 25% (may be reached by transfusion)

- White blood cell count >= 2.5 x 10^3/mm^3

- Absolute granulocyte count >= 1.2 x 10^3/mm^3

- Platelets >= 100 x 10^3/mm^3 (or >= lower limit of institutional normal value)

- Calculated creatinine clearance (Cr Cl) >= 50 ml/min; eligible for full dose

- Calculated Cr Cl >= 30 ml/min; eligible for reduced dose methotrexate

- Bilirubin =< 2.0 x upper limit of institutional normal value

- The subject may have had other systemic chemotherapy for PCNSL during the 90 days
since PCNSL diagnosis; prior systemic chemotherapy must have been given at least 4
weeks prior to study entry (6 weeks for nitrosourea agents), with the exceptions of
methotrexate and rituximab which may have been given at least 10 days prior; ocular
lymphoma treatment may have been given any time prior to study entry; if the subject
has undergone treatment for parenchymal disease and the parenchymal disease has
progressed on a stable or increasing dose of steroids, the subject is not eligible for

- Sexually active women of child-bearing potential and men must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to study
treatment and for the duration of study treatment; should a woman become pregnant or
suspect she is pregnant while participating in this study, she should inform her
treating physician immediately

- Subjects with a bone marrow biopsy which shows microscopic, low-level involvement of
lymphoma are eligible

- Subject with seropositivity for hepatitis B or hepatitis C must be cleared by
hepatology service prior to participating in treatment protocol

Exclusion Criteria:

- Prior cranial or spinal radiotherapy

- Subjects with radiographic signs of excessive intra-cranial mass effect with
associated rapid neurologic deterioration, and/or spinal block, are unsafe to undergo
BBBD chemotherapy and are not eligible

- Uncontrolled (over the last 30 days), clinically significant confounding medical

- Seropositivity for the human immunodeficiency virus

- Systemic lymphoma

- Subjects who have a positive serum human chorionic gonadotropin (hCG), are pregnant or
lactating are ineligible

- Known allergy to any of the study agents

- Subjects who are at significant risk for general anesthesia
We found this trial at
Cincinnati, Ohio 45220
Principal Investigator: Robert E. Albright
Phone: 859-301-5473
Cincinnati, OH
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2049 E 100th St
Cleveland, Ohio 44106
(216) 444-2200
Principal Investigator: David M. Peereboom
Phone: 216-445-6068
Cleveland Clinic Foundation The Cleveland Clinic (formally known as The Cleveland Clinic Foundation) is a...
Cleveland, OH
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Columbus, Ohio 43210
Principal Investigator: Edward A. Neuwelt
Phone: 503-494-5626
Columbus, OH
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3181 S.W. Sam Jackson Park Road
Portland, Oregon 97239
503 494-7999
Principal Investigator: Edward A. Neuwelt
Phone: 503-494-5626
OHSU Knight Cancer Institute OHSU Knight Cancer Institute is known worldwide for our contributions to...
Portland, OR
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