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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2015 by OHSU Knight Cancer Institute
Sponsor:
Collaborator:
Information provided by (Responsible Party):
OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:
NCT00293475
First received: February 16, 2006
Last updated: August 20, 2015
Last verified: August 2015
  Purpose

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.


Condition Intervention Phase
Central Nervous System Lymphoma
Drug: Carboplatin
Drug: Mannitol
Drug: Methotrexate
Other: Quality-of-Life Assessment
Biological: Rituximab
Drug: Sodium Thiosulfate
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by OHSU Knight Cancer Institute:

Primary Outcome Measures:
  • CR rate (Phase II) [ Time Frame: Within the first 3 months of treatment ] [ Designated as safety issue: No ]
  • Incidence of toxicities, assessed using National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0 (Phase I) [ Time Frame: Within 2 months of completion of study treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Event-free survival [ Time Frame: From entry onto study until death or progression of disease, assessed at 2 years ] [ Designated as safety issue: No ]
    Kaplan-Meier estimates of these survival distributions will be plotted. Descriptive stratifications of these survival distributions by baseline characteristics will be evaluated using the log-rank statistic. If there are multiple predictors of these outcomes, Cox proportional hazard models will be fit to these data to determine which predictors are independent of others in a multi-variable model.

  • Overall survival [ Time Frame: From entry onto study until death from any cause, assessed at 2 years ] [ Designated as safety issue: No ]
    Kaplan-Meier estimates of these survival distributions will be plotted. Descriptive stratifications of these survival distributions by baseline characteristics will be evaluated using the log-rank statistic. If there are multiple predictors of these outcomes, Cox proportional hazard models will be fit to these data to determine which predictors are independent of others in a multi-variable model.


Estimated Enrollment: 81
Study Start Date: October 2005
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (rituximab, mannitol, methotrexate, carboplatin)
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.
Drug: Carboplatin
Given IA
Other Names:
  • Blastocarb
  • Carboplat
  • CARBOPLATIN
  • Carboplatin Hexal
  • Carboplatino
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplat
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo
Drug: Mannitol
Given IA
Other Names:
  • D-Mannitol
  • MANNITOL
  • Mannitol, D-
  • Osmitrol
  • Resectisol
Drug: Methotrexate
Given IA
Other Names:
  • Abitrexate
  • Alpha-Methopterin
  • Amethopterin
  • Brimexate
  • CL 14377
  • CL-14377
  • Emtexate
  • Emthexat
  • Emthexate
  • Farmitrexat
  • Fauldexato
  • Folex
  • Folex PFS
  • Lantarel
  • Ledertrexate
  • Lumexon
  • Maxtrex
  • Medsatrexate
  • Metex
  • Methoblastin
  • METHOTREXATE
  • Methotrexate LPF
  • Methotrexate Methylaminopterin
  • Methotrexatum
  • Metotrexato
  • Metrotex
  • Mexate
  • Mexate-AQ
  • MTX
  • Novatrex
  • Rheumatrex
  • Texate
  • Tremetex
  • Trexeron
  • Trixilem
  • WR-19039
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Biological: Rituximab
Given IV
Other Names:
  • BI 695500
  • C2B8 Monoclonal Antibody
  • Chimeric Anti-CD20 Antibody
  • IDEC-102
  • IDEC-C2B8
  • IDEC-C2B8 Monoclonal Antibody
  • MabThera
  • Monoclonal Antibody IDEC-C2B8
  • PF-05280586
  • Rituxan
  • RITUXIMAB
  • Rituximab Biosimilar BI 695500
  • Rituximab Biosimilar PF-05280586
  • Rituximab Biosimilar RTXM83
  • RTXM83
Drug: Sodium Thiosulfate
Given IV
Other Names:
  • Cyanide Antidote Package
  • Disodium Thiosulfate
  • S-Hydril
  • Sodium Hyposulfate
  • SODIUM THIOSULFATE
  • Sodium Thiosulfate Pentahydrate
  • Sodium Thiosulphate
  • Sodothiol
  • Thiosulfate, Sodium, Pentahydrate
  • Thiosulfuric Acid Disodium Salt

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

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, Minnesota
University of Minnesota Medical Center-Fairview Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Edward A. Neuwelt    503-494-5626    neuwelte@ohsu.edu   
Principal Investigator: Edward A. Neuwelt         
United States, Ohio
Good Samaritan Hospital - Cincinnati Recruiting
Cincinnati, Ohio, United States, 45220
Contact: Robert E. Albright    859-301-5473    darla.hehman@stelizabeth.com   
Principal Investigator: Robert E. Albright         
Cleveland Clinic Foundation Recruiting
Cleveland, Ohio, United States, 44195
Contact: David M. Peereboom    216-445-6068    peerebd@ccf.org   
Principal Investigator: David M. Peereboom         
United States, Oregon
OHSU Knight Cancer Institute Recruiting
Portland, Oregon, United States, 97239
Contact: Edward A. Neuwelt    503-494-5626    neuwelte@ohsu.edu   
Principal Investigator: Edward A. Neuwelt         
Sponsors and Collaborators
OHSU Knight Cancer Institute
Investigators
Principal Investigator: Edward Neuwelt OHSU Knight Cancer Institute
  More Information

No publications provided

Responsible Party: OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier: NCT00293475     History of Changes
Other Study ID Numbers: 1012, NCI-2013-00787, CR00022596, HEM-08059-LX, MR00041596, SOL-05025-L, SOL-05025-LM, MR00045915, 1012, P30CA069533, R01CA137488
Study First Received: February 16, 2006
Last Updated: August 20, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Antibodies
Antibodies, Monoclonal
Carboplatin
Immunoglobulins
Mannitol
Methotrexate
Rituximab
Sodium thiosulfate
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Anti-Bacterial Agents
Anti-Infective Agents
Antidotes
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antioxidants
Antirheumatic Agents
Antitubercular Agents
Cardiovascular Agents
Chelating Agents
Dermatologic Agents
Diuretics

ClinicalTrials.gov processed this record on August 27, 2015