Treating Patients With Recurrent PCNSL With Carboplatin/BBBD and Adding Rituxan To The Treatment Regimen

NCT ID: NCT00074165

Last Updated: 2023-07-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-01-31
• Study Completion Date: 2010-12-31

Brief Summary

RATIONALE: Monoclonal antibodies, such as rituximab, can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as carboplatin, cyclophosphamide, etoposide, etoposide phosphate, and cytarabine, use different ways to stop cancer cells from dividing so they stop growing or die. Osmotic blood-brain barrier disruption uses certain drugs to open the blood vessels around the brain and allow anticancer substances to be delivered directly to the brain tumor. Chemoprotective drugs such as sodium thiosulfate may protect normal cells from the side effects of carboplatin-based chemotherapy. Combining rituximab with chemotherapy given with osmotic blood-brain barrier disruption plus sodium thiosulfate may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combining rituximab with combination chemotherapy given with osmotic blood-brain barrier disruption plus sodium thiosulfate in treating patients who have refractory or recurrent primary CNS lymphoma.

Detailed Description

OBJECTIVES:

Primary

• Determine the efficacy of rituximab, carboplatin, cyclophosphamide, etoposide or etoposide phosphate and cytarabine administered in conjunction with osmotic blood-brain barrier disruption and high-dose sodium thiosulfate, in terms of complete response rate, in patients with refractory or recurrent primary CNS lymphoma.

Secondary

• Determine the overall survival and 2-year progression-free survival of patients treated with this regimen.
• Determine the quality of life and cognitive function of patients treated with this regimen.
• Determine the neurotoxicity of this regimen in these patients.
• Determine the percentage of patients with ototoxicity over time after treatment with this regimen.
• Determine the effect of delayed administration of sodium thiosulfate on granulocyte and erythrocyte counts in these patients.

OUTLINE: This is a multicenter study.

Patients receive rituximab IV on day 1. On days 2 and 3, patients receive carboplatin intra-arterially over 10 minutes, cyclophosphamide IV over 10 minutes, and etoposide or etoposide phosphate IV over 10 minutes in conjunction with blood-brain barrier disruption. Patients also receive high-dose sodium thiosulfate IV over 15 minutes administered 4 and 8 hours after carboplatin on days 2 and 3 and intraventricular or intrathecal cytarabine on day 14. Beginning 48 hours after the last dose of chemotherapy, patients receive filgrastim (G-CSF)* subcutaneously (SC) daily for 7-10 days or until blood counts recover. Treatment repeats every 4 weeks for up to 12 courses.

NOTE: * Alternatively, patients may receive a single dose of pegfilgrastim SC, administered 48 hours after the completion of chemotherapy

Patients with intraocular lymphoma also receive methotrexate intravitreally twice weekly until the vitreous is clear of cells by slit lamp exam; once weekly for 1 month; and then monthly for 1 year.

Quality of life is assessed at baseline, every 3 months during treatment, within 30 days of final treatment, then every 6 months for 1 year, and then annually thereafter.

Patients are followed monthly for 3 months, every 2 months for 8 months, every 3 months for 1 year, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 11-25 patients will be accrued for this study within 7-10 years.

Conditions

Brain and Central Nervous System Tumors; Drug/Agent Toxicity by Tissue/Organ; Lymphoma; Thrombocytopenia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

All subjects

Group Type: EXPERIMENTAL

Rituxan

Intervention Type: DRUG

Total dose: 375mg/m2 infused IV; Every 4 weeks for up to one year.

Cyclophosphamide

Intervention Type: DRUG

Dose 330mg/m2 x 2 days infused IV; Every 4 weeks for up to 1 year

Etoposide

Intervention Type: DRUG

Dose 200mg/m2 x 2 days infused IV; Every 4 weeks for up to one year. Etoposide phosphate may be given instead.

Etoposide phosphate

Intervention Type: DRUG

Dose 200mg/m2 infused IV x 2 days; Every 4 weeks for up to one year. Etoposide may be given instead.

Carboplatin

Intervention Type: DRUG

Dose: 200mg/m2 x 2 days infused IA with BBBD; Every 4 weeks for up to one year.

Sodium thiosulfate

Intervention Type: DRUG

Dose: 4 hrs post carboplatin = 20gm/m2;

Dose: 8 hrs post carboplatin = 16gm/m2

Infused IV x 2 days

Neupogen

Intervention Type: DRUG

48 hours after chemotherapy, QD x 7-10 days until WBC greater than 5000. Neulasta (Pegfilgrastim) may be given instead.

Neulasta

Intervention Type: DRUG

Dose: 6mg, 24-72 hours after chemotherapy. Neupogen may be given instead.

Cytarabine

Intervention Type: DRUG

Dose: 40mg on Day 14 following chemotherapy

Interventions

Rituxan

Total dose: 375mg/m2 infused IV; Every 4 weeks for up to one year.

Intervention Type: DRUG

Cyclophosphamide

Dose 330mg/m2 x 2 days infused IV; Every 4 weeks for up to 1 year

Intervention Type: DRUG

Etoposide

Dose 200mg/m2 x 2 days infused IV; Every 4 weeks for up to one year. Etoposide phosphate may be given instead.

Intervention Type: DRUG

Etoposide phosphate

Dose 200mg/m2 infused IV x 2 days; Every 4 weeks for up to one year. Etoposide may be given instead.

Intervention Type: DRUG

Carboplatin

Dose: 200mg/m2 x 2 days infused IA with BBBD; Every 4 weeks for up to one year.

Intervention Type: DRUG

Sodium thiosulfate

Dose: 4 hrs post carboplatin = 20gm/m2;

Dose: 8 hrs post carboplatin = 16gm/m2

Infused IV x 2 days

Intervention Type: DRUG

Neupogen

48 hours after chemotherapy, QD x 7-10 days until WBC greater than 5000. Neulasta (Pegfilgrastim) may be given instead.

Intervention Type: DRUG

Neulasta

Dose: 6mg, 24-72 hours after chemotherapy. Neupogen may be given instead.

Intervention Type: DRUG

Cytarabine

Dose: 40mg on Day 14 following chemotherapy

Intervention Type: DRUG

Other Intervention Names

Rituximab; STS; G-CSF; filgrastim; Pegfilgrastim

Eligibility Criteria

Inclusion Criteria

• Signed informed consent form in accordance with institutional guidelines
• Histologically or cytologically confirmed primary CNS lymphoma documented by brain biopsy or cerebrospinal fluid or vitrectomy analysis
• CD20 positive disease
• Progressive or relapsed disease during or after completion of prior methotrexate-based chemotherapy
• Aged 18 months to 75 years
• Performance status ECOG 0-3 OR Karnofsky 30-100%
• Hematocrit at least 25% (transfusion or epoetin alfa allowed)
• Absolute granulocyte count at least 1,200/mm^3
• Platelet count at least 100,000/mm^3 OR at least lower limit of normal
• Bilirubin no greater than 2.0 times upper limit of normal
• Creatinine less than 1.8 mg/dL
• Calculated Creatinine clearance (CrCl) at least 50 mL/min
• Adequate cardiac function to tolerate general anesthesia
• Adequate pulmonary function to tolerate general anesthesia
• Available for follow-up for 1 year post therapy
• Fertile patients must use effective contraception for a minimum of 2 months before and during study participation

Exclusion Criteria

• Radiographic signs of intra-cranial herniation and/or spinal block
• HIV positive
• Systemic lymphoma
• Positive serum HCG, pregnant or lactating
• Allergy to study agents
• Hepatitis B or hepatitis C positive

• Minimum Eligible Age: 18 Months
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

OHSU Knight Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Edward Neuwelt

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Edward A. Neuwelt, MD

Role: PRINCIPAL_INVESTIGATOR

OHSU Knight Cancer Institute

Locations

Good Samaritan Hospital Cancer Treatment Center, Hatton Institute

Cincinnati, Ohio, United States

Knight Cancer Institute at Oregon Health and Science University

Portland, Oregon, United States

Countries

United States

Other Identifiers

5R01CA137488-15

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ONC-02059-LX

Identifier Type: OTHER

Identifier Source: secondary_id

641

Identifier Type: OTHER

Identifier Source: secondary_id

7465

Identifier Type: OTHER

Identifier Source: secondary_id

OHSU-641

Identifier Type: OTHER

Identifier Source: secondary_id

IRB00000641

Identifier Type: -

Identifier Source: org_study_id

NCT00261651

Identifier Type: -

Identifier Source: nct_alias