Rituximab&Methotrexate Chemotherapy w/Blood-Brain Barrier Disruption (BBBD) & Sodium Thiosulfate Chemoprotection for Patients With Newly Diagnosed PCNSL

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 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: May 2, 2014
Last verified: May 2014
  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. Chemotherapy drugs 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 mannitol, to open tight junctions in the blood vessels in the brain and allow methotrexate and carboplatin to be carried to tumor. Giving rituximab together with blood-brain barrier disruption and methotrexate-based 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 and methotrexate with blood-brain barrier disruption and delayed sodium thiosulfate chemoprotection to see how well they work in treating patients with newly diagnosed primary central nervous system lymphoma.


Condition Intervention Phase
Primary Central Nervous System Lymphoma
Brain and Central Nervous System Tumors
Lymphoma
Drug: Rituxan
Drug: Carboplatin
Drug: Methotrexate
Drug: Sodium thiosulfate
Drug: Neupogen
Drug: Neulasta
Drug: Leucovorin
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 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

Resource links provided by NLM:


Further study details as provided by OHSU Knight Cancer Institute:

Primary Outcome Measures:
  • Complete response rate [ Time Frame: first 3 months of treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival at 2 years [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Event-free survival at 2 years [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 81
Study Start Date: December 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: Rituximab, Methotrexate and Carboplatin

Rituximab (total dose 375mg/m2) will be administered i.v. per institutional guidelines within 24 hours prior to the first BBBD of each monthly course.

Methotrexate 2500 mg/day x 2 days (total dose 5000mg); (1250mg if Creatinine Clearance (CrCl) ≤ 50, but ≥ 30 ml/min) will be infused i.a.. Methotrexate will be infused over 10 minutes in 180 cc normal saline beginning immediately after the mannitol infusion.

carboplatin (200mg/m2/day x 2 days; total dose 400 mg/m2) will be infused i.a.over 10 minutes, in 180 cc of normal saline.

Drug: Rituxan
Total dose: 375mg/m2; Every 4 weeks for up to one year.
Other Name: rituximab
Drug: Carboplatin
Dose 200mg/m2/day x 2 days; Every 4 weeks for up to one year
Drug: Methotrexate
Dose 2500mg/day x 2 days; Every 4 weeks for up to one year
Drug: Sodium thiosulfate
Dose: 4 hrs post carboplatin = 20gm/m2; Dose: 8 hrs post carboplatin = 16gm/m2
Other Name: STS
Drug: Neupogen
48 hrs after last dose of methotrexate, every day (QD) x 7-10 days until white blood cells (WBC) greater than 5000. Dose based on weight of subject. Neulasta (Pegfilgrastim) may be given instead.
Other Names:
  • G-CSF
  • filgrastim
Drug: Neulasta
Dose: 6mg, 24-72 hours after chemotherapy. Neupogen may be given instead.
Other Name: Pegfilgrastim
Drug: Leucovorin
80mg i.v. at 36 hours after first dose of methotrexate; then 50mg p.o. or i.v. every 6 hours for 20 doses. Additional dosing requirements may apply as clinically indicated.

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/II study

  • Patients receive rituximab IV 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 and/or rituximab into the eye(s) up to twice a week until the vitreous is clear of cancer cells and then as determined by the ophthalmologist.
  • 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.
  Eligibility

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

INCLUSION CRITERIA:

  • Signed written informed consent form
  • Histopathologic confirmation of intermediate- or high-grade 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
  • No radiographic signs of excessive intracranial mass effect with associated rapid neurologic deterioration and/or spinal block
  • Eastern Cooperative Oncology Group (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 and carboplatin)
  • Bilirubin ≤ 2.0 times upper limit of normal
  • Fertile patients must use effective contraception
  • Other chemotherapy for PCNSL during the 90 days since diagnosis allowed
  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas and at least 10 days since prior methotrexate)
  • Available for follow-up for at least one year after completion of treatment

EXCLUSION CRITERIA:

  • Prior cranial or spinal radiotherapy
  • Systemic lymphoma
  • Seropositive for HIV
  • Seropositive for hepatitis B or hepatitis C
  • Uncontrolled, clinically significant confounding medical conditions within the past 30 days
  • Pregnant or nursing
  • Allergy to any of the study agents (rituximab, carboplatin, methotrexate, or sodium thiosulfate)
  • If subject has Congestive Heart Failure (CHF), New York Heart Association class III or IV
  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

Contacts
Contact: Edward A Neuwelt, MD 503-494-5626 neuwelte@ohsu.edu
Contact: Cynthia A Lacy, BSN 503-494-5626 lacyc@ohsu.edu

Locations
United States, Oregon
Oregon Health and Science University Recruiting
Portland, Oregon, United States, 97239-3098
Contact: Edward A Neuwelt, MD    503-494-5626    neuwelte@ohsu.edu   
Contact: Cynthia A Lacy, BSN    503-494-5626    lacyc@ohsu.edu   
Principal Investigator: Edward A Neuwelt, MD         
Sponsors and Collaborators
OHSU Knight Cancer Institute
Investigators
Principal Investigator: Edward A. Neuwelt, MD Oregon Health and Science University
  More Information

Additional Information:
No publications provided

Responsible Party: OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier: NCT00293475     History of Changes
Other Study ID Numbers: OHSU-1012, 3R01CA137488, 1012, SOL-05025-L
Study First Received: February 16, 2006
Last Updated: May 2, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by OHSU Knight Cancer Institute:
drug/agent toxicity by tissue/organ
primary central nervous system non-Hodgkin lymphoma
primary central nervous system Hodgkin lymphoma
intraocular lymphoma

Additional relevant MeSH terms:
Central Nervous System Neoplasms
Lymphoma
Nervous System Neoplasms
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Nervous System Diseases
Carboplatin
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
Chelating Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists

ClinicalTrials.gov processed this record on October 22, 2014