Methotrexate, Mannitol, Rituximab, and Carboplatin in Treating Patients With Newly Diagnosed Primary Central Nervous System Lymphoma
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
9 other identifiers
interventional
81
1 country
4
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Oct 2005
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
Study Start
First participant enrolled
October 14, 2005
CompletedFirst Submitted
Initial submission to the registry
February 16, 2006
CompletedFirst Posted
Study publicly available on registry
February 17, 2006
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 31, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
January 31, 2023
CompletedSeptember 22, 2021
September 1, 2021
16.3 years
February 16, 2006
September 15, 2021
Conditions
Outcome Measures
Primary Outcomes (2)
Incidence of toxicities, assessed using National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0 (Phase I)
Within 2 months of completion of study treatment
CR rate (Phase II)
Within the first 3 months of treatment
Secondary Outcomes (2)
Overall survival
From entry onto study until death from any cause, assessed at 2 years
Event-free survival
From entry onto study until death or progression of disease, assessed at 2 years
Study Arms (1)
Treatment (rituximab, mannitol, methotrexate, carboplatin)
EXPERIMENTALPatients 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.
Interventions
Given IA
Given IA
Given IA
Ancillary studies
Given IV
Given IV
Eligibility Criteria
You may qualify if:
- 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) (performed within 14 days of registration)
- White blood cell count \>= 2.5 x 10\^3/mm\^3 (performed within 14 days of registration)
- Absolute granulocyte count \>= 1.2 x 10\^3/mm\^3 (performed within 14 days of registration)
- Platelets \>= 100 x 10\^3/mm\^3 (or \>= lower limit of institutional normal value) (performed within 14 days of registration)
- Calculated creatinine clearance (Cr Cl) \>= 50 ml/min (performed within 14 days of registration); eligible for full dose methotrexate
- Calculated Cr Cl \>= 30 ml/min (performed within 14 days of registration); eligible for reduced dose methotrexate
- Bilirubin =\< 2.0 x upper limit of institutional normal value (performed within 14 days of registration)
- 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 enrollment
- 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
You may not qualify if:
- 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 conditions
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- OHSU Knight Cancer Institutelead
- National Cancer Institute (NCI)collaborator
- Oregon Health and Science Universitycollaborator
Study Sites (4)
Good Samaritan Hospital - Cincinnati
Cincinnati, Ohio, 45220, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
OHSU Knight Cancer Institute
Portland, Oregon, 97239, United States
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Edward A Neuwelt
OHSU Knight Cancer Institute
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
February 16, 2006
First Posted
February 17, 2006
Study Start
October 14, 2005
Primary Completion
January 31, 2022
Study Completion
January 31, 2023
Last Updated
September 22, 2021
Record last verified: 2021-09