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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 survival

Overall 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

Page last updated: August 23, 2015

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