Rituximab, Mannitol, Combination Chemotherapy, and Sodium Thiosulfate in Treating Patients With Newly Diagnosed Primary Central Nervous System Lymphoma - Full Text View

Sponsors and Collaborators:	Oregon Health and Science University National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00293475

Purpose

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as methotrexate, carboplatin, and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.

Chemoprotective drugs, such as sodium thiosulfate, may protect normal cells from the side effects of chemotherapy. Osmotic blood-brain barrier disruption uses certain drugs, such as mannitol, to open the blood vessels around the brain and allow methotrexate and carboplatin to be carried directly to the brain. Giving rituximab together with mannitol and combination chemotherapy may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of carboplatin when given together with rituximab, mannitol, methotrexate, and sodium thiosulfate and to see how well they work in treating patients with newly diagnosed primary central nervous system lymphoma.

Condition	Intervention	Phase
Cancer-Related Problem/Condition Lymphoma	Biological: filgrastim Biological: pegfilgrastim Biological: rituximab Drug: carboplatin Drug: cytarabine Drug: mannitol Drug: methotrexate Drug: sodium thiosulfate	Phase I Phase II

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Methotrexate Mannitol Cytarabine hydrochloride Sodium thiosulfate Carboplatin Filgrastim Rituximab Pegfilgrastim Cytarabine Sodium hyposulfite

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	A Phase I/II Study of Patient 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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Complete response rate [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall survival at 2 years [ Designated as safety issue: No ]
Event-free survival at 2 years [ Designated as safety issue: No ]

Estimated Enrollment:	81
Study Start Date:	December 2005
Estimated Primary Completion Date:	January 2010 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Evaluate the safety and toxicities of rituximab in combination with blood-brain barrier disruption with mannitol, combination chemotherapy comprising methotrexate and carboplatin, and delayed sodium thiosulfate.
Determine the effect of this regimen on complete response (CR) rate within the first 3 months of treatment in these patients.

Secondary

Estimate the overall CR response rate, the 2-year overall survival, and the 2-year event-free survival of these patients.

OUTLINE: This is a multicenter, phase I, dose-de-escalation study of carboplatin followed by an open-label, phase II study.

Phase I: Patients receive rituximab IV over 5 hours on day 1 followed by blood-brain barrier disruption comprising mannitol intra-arterially (IA) and combination chemotherapy comprising methotrexate IA over 10 minutes and carboplatin IA over 10 minutes on days 2 and 3. Patients also receive sodium thiosulfate IV over 15 minutes twice on days 2 and 3 and filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 5 and continuing for approximately 7-10 days or until blood counts recover OR pegfilgrastim SC once on day 5. Patients with positive cerebrospinal fluid (CSF) cytology also receive cytarabine via Ommaya reservoir or lumbar puncture on day 14. Patients with ocular involvement also receive injections of methotrexate into the eye(s) twice a week until the vitreous is clear of cancer cells and then once a week for 1 month and once a month for up to 1 year.

Cohorts of 3-6 patients receive de-escalating doses of carboplatin until the phase II dose is determined. The phase II dose is defined as the dose at which 0 of 3 or 1 of 6 patients experience dose-limiting toxicity.

Phase II: Patients receive therapy as in phase I, including carboplatin at the phase II dose.

Quality of life is assessed at baseline, every 6 months during treatment, at completion of treatment, and then every 3 months for 2 years, every 6 months for 3 years, and annually thereafter.

PROJECTED ACCRUAL: A total of 81 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histopathologic confirmation of intermediate- or high-grade non-AIDS-related primary central nervous system lymphoma (PCNSL) as documented by brain biopsy or cytology (analysis from cerebrospinal fluid [CSF] or vitrectomy)
- Diagnosed within the past 90 days
CD20-positive disease
Tumor should be characterized by immunophenotype
No radiographic signs of excessive intracranial mass effect with associated rapid neurologic deterioration and/or spinal block
No systemic lymphoma

PATIENT CHARACTERISTICS:

ECOG performance status (PS) 0-3 OR Karnofsky PS 40-100%
Hematocrit ≥ 25% (transfusion allowed)
WBC ≥ 2,500/mm^3
Absolute granulocyte count ≥ 1,200/mm^3
Platelet count ≥ 100,000/mm^3 (or ≥ lower limit of normal)
Creatinine clearance ≥ 50 mL/min (eligible for full-dose methotrexate)
Creatinine clearance ≥ 30 mL/min (eligible for reduced-dose methotrexate)
Bilirubin ≤ 2.0 times upper limit of normal
New York Heart Association class I or II
No uncontrolled, clinically significant confounding medical conditions within the past 30 days
No HIV positivity
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No known allergy to any of the study agents
No seropositivity for hepatitis B or hepatitis C

PRIOR CONCURRENT THERAPY:

Other chemotherapy for PCNSL during the 90 days since diagnosis allowed
At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
- At least 10 days since prior methotrexate
No prior cranial or spinal radiotherapy
Prior surgery or biopsy allowed

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00293475

Locations

United States, Ohio
Cleveland Clinic Cancer Center at Fairview Hospital	Recruiting
Cleveland, Ohio, United States, 44111
Contact: Clinical Trials Office - Cleveland Clinic Cancer Center at Fai 216-476-9362
Good Samaritan Hospital Cancer Treatment Center	Recruiting
Cincinnati, Ohio, United States, 45220
Contact: Robert E. Albright, MD 513-936-5370 ralbright@ohcmail.com
United States, Oregon
Knight Cancer Institute at Oregon Health and Science University	Recruiting
Portland, Oregon, United States, 97239-3098
Contact: Clinical Trials Office - Knight Cancer Institute at Oregon Hea 503-494-1080 trials@ohsu.edu

Sponsors and Collaborators

Oregon Health and Science University

National Cancer Institute (NCI)

Investigators

Study Chair:

Edward A. Neuwelt, MD

Oregon Health and Science University

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000459744, OHSU-1012, OHSU-SOL-05025-L
Study First Received:	February 16, 2006
Last Updated:	April 2, 2009
ClinicalTrials.gov Identifier:	NCT00293475 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

drug/agent toxicity by tissue/organ
primary central nervous system lymphoma
intraocular lymphoma

Study placed in the following topic categories:

Antimetabolites
Antioxidants
Immunologic Factors
Diuretics
Central Nervous System Lymphoma, Primary
Anti-Bacterial Agents
Mannitol
Methotrexate
Lymphoma
Cytarabine
Immunoglobulins
Immunoproliferative Disorders
Rituximab

Sodium thiosulfate
Carboplatin
Cardiovascular Agents
Folic Acid Antagonists
Antiviral Agents
Immunosuppressive Agents
Folic Acid
Lymphatic Diseases
Antibodies
Chelating Agents
Antitubercular Agents
Lymphoproliferative Disorders
Antirheumatic Agents

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Antioxidants
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Diuretics
Physiological Effects of Drugs
Reproductive Control Agents
Anti-Bacterial Agents
Mannitol
Therapeutic Uses
Abortifacient Agents
Methotrexate

Dermatologic Agents
Lymphoma
Nucleic Acid Synthesis Inhibitors
Cytarabine
Antidotes
Immunoproliferative Disorders
Neoplasms by Histologic Type
Immune System Diseases
Rituximab
Diuretics, Osmotic
Sodium thiosulfate
Enzyme Inhibitors
Cardiovascular Agents
Carboplatin
Folic Acid Antagonists

ClinicalTrials.gov processed this record on May 07, 2009