Methotrexate, Mannitol, Rituximab, and Carboplatin in Treating Patients With Newly Diagnosed Primary Central Nervous System Lymphoma
Information source: OHSU Knight Cancer Institute
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Central Nervous System Lymphoma
Intervention: Carboplatin (Drug); Mannitol (Drug); Methotrexate (Drug); Quality-of-Life Assessment (Other); Rituximab (Biological); Sodium Thiosulfate (Drug)
Phase: Phase 1/Phase 2
Status: Recruiting
Sponsored by: OHSU Knight Cancer Institute Official(s) and/or principal investigator(s): Edward Neuwelt, Principal Investigator, Affiliation: OHSU Knight Cancer Institute
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.
Clinical Details
Official title: 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
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: CR rate (Phase II)Incidence of toxicities, assessed using National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0 (Phase I)
Secondary outcome: Event-free survivalOverall survival
Detailed description:
PRIMARY OBJECTIVES:
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 (IV).
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%.
SECONDARY OBJECTIVES:
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.
OUTLINE:
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.
Eligibility
Minimum age: 18 Years.
Maximum age: 75 Years.
Gender(s): Both.
Criteria:
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
methotrexate
- 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 exception 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 and disease has progressed, 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
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
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
Locations and Contacts
University of Minnesota Medical Center-Fairview, Minneapolis, Minnesota 55455, United States; Recruiting Edward A. Neuwelt, Phone: 503-494-5626, Email: neuwelte@ohsu.edu Edward A. Neuwelt, Principal Investigator
Good Samaritan Hospital - Cincinnati, Cincinnati, Ohio 45220, United States; Recruiting Robert E. Albright, Phone: 859-301-5473, Email: darla.hehman@stelizabeth.com Robert E. Albright, Principal Investigator
Cleveland Clinic Foundation, Cleveland, Ohio 44195, United States; Recruiting David M. Peereboom, Phone: 216-445-6068, Email: peerebd@ccf.org David M. Peereboom, Principal Investigator
OHSU Knight Cancer Institute, Portland, Oregon 97239, United States; Recruiting Edward A. Neuwelt, Phone: 503-494-5626, Email: neuwelte@ohsu.edu Edward A. Neuwelt, Principal Investigator
Additional Information
Starting date: October 2005
Last updated: August 20, 2015
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