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
18 Years
75 Years
Both
Brain and Central Nervous System Tumors, Lymphoma
Trial Information
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
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 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.
- 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.
Inclusion 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
- 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
- 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 CHF, New York Heart Association class III or IV
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Complete response rate
Outcome Time Frame:
first 3 months of treatment
Safety Issue:
No
Principal Investigator
Edward A. Neuwelt, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Oregon Health and Science University
Authority:
United States: Institutional Review Board
Study ID:
OHSU-1012
NCT ID:
NCT00293475
Start Date:
December 2005
Completion Date:
December 2014
Related Keywords:
- Brain and Central Nervous System Tumors
- Lymphoma
- drug/agent toxicity by tissue/organ
- primary central nervous system non-Hodgkin lymphoma
- primary central nervous system Hodgkin lymphoma
- intraocular lymphoma
- Lymphoma
- Nervous System Neoplasms
- Central Nervous System Neoplasms
Name | Location |
|---|---|
| Oregon Health and Science University | Portland, Oregon 97201 |
| Good Samaritan Hospital, Hatton Institute | Cincinnati, Ohio 45220 |
