Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Rituximab, Carboplatin, Cyclophosphamide, and Etoposide or Etoposide Phosphate Given With Osmotic Blood-Brain Barrier Disruption Plus Sodium Thiosulfate and Cytarabine in Treating Patients With Refractory or Recurrent Primary CNS Lymphoma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Supportive care, Treatment	Active	18 months to 75 years	NCI	OHSU-7465 OHSU-641, OHSU-ONC-02059-LX, NCT00074165

Objectives

Primary

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

Secondary

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

Entry Criteria

Disease Characteristics:

• 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



• No systemic lymphoma

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• Prior radiotherapy allowed

Surgery

• Prior surgery or biopsy allowed

Patient Characteristics:

Age

• 18 months to 75 years

Performance status

• ECOG 0-3

  OR

• Karnofsky 30-100%

Life expectancy

• Not specified

Hematopoietic

• Hematocrit at least 25% (transfusion or epoetin alfa allowed)
• Absolute granulocyte count at least 1,200/mm³
• Platelet count at least 100,000/mm³ OR at least lower limit of normal

Hepatic

• Bilirubin no greater than 2.0 times upper limit of normal

Renal

• Creatinine less than 1.8 mg/dL
• Creatinine clearance at least 30 mL/min

Cardiovascular

• Adequate cardiac function to tolerate general anesthesia

Pulmonary

• Adequate pulmonary function to tolerate general anesthesia

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception for 2 months before and during study participation
• No known allergy to study agents
• HIV negative

Expected Enrollment

A total of 11-25 patients will be accrued for this study within 2-3 years.

Outcomes

Efficacy (complete response rate) of chemotherapy regimen assessed by radiographic response at 2 years

Overall survival assessed by clinical and radiographic response
Progression-free survival assessed by clinical and radiographic response from first day of treatment until tumor progression
Quality of life assessed by EORTC QOL before treatment and then every 3 months
Ototoxicity assessed by audiology hearing test done monthly during treatment
Effect of sodium thiosulfate (STS) on granulocytes and erythrocytes assessed by complete blood count lab values done weekly during treatment
Measure concentration of rituximab in serum and cerebrospinal fluid by rituximab test assay once at the start of treatment

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, at 30 days, 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.

Trial Contact Information

Trial Lead Organizations

Knight Cancer Institute at Oregon Health and Science University

Edward Neuwelt, MD, Principal investigator		Ph: 503-494-5626; 800-494-1234 Email: Neuwelte@ohsu.edu

U.S.A.
Ohio
	Cincinnati
	Good Samaritan Hospital Cancer Treatment Center
		Robert Albright, MD	Ph:  513-936-5370
			Email: ralbright@ohcmail.com
	Cleveland
	Cleveland Clinic Taussig Cancer Center
		Clinical Trials Office - Cleveland Clinic Taussig Cancer Center	Ph:  866-223-8100
	Columbus
	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
		Ohio State University Cancer Clinical Trial Matching Service	Ph:  866-627-7616
			Email: osu@emergingmed.com
Oregon
	Portland
	Knight Cancer Institute at Oregon Health and Science University
		Clinical Trials Office - Knight Cancer Institute at Oregon Health and Science University	Ph:  503-494-1080
			Email: trials@ohsu.edu

Registry Information
Official Title		A Phase II Trial Involving Patients With Recurrent PCNSL Treated With Carboplatin/BBBD, by Adding Rituxan (Rituximab), An Anti CD-20 Antibody, To The Treatment Regimen
Trial Start Date		2003-01-03
Trial Completion Date		2009-06-04 (estimated)
Registered in ClinicalTrials.gov		NCT00074165
Date Submitted to PDQ		2003-10-28
Information Last Verified		2009-06-25
NCI Grant/Contract Number		CA69533

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