Treating Patients With Recurrent PCNSL With Carboplatin/BBBD and Adding Rituxan To The Treatment Regimen - Full Text View

Sponsor:	OHSU Knight Cancer Institute
Collaborator:	National Cancer Institute (NCI)
Information provided by (Responsible Party):	OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:	NCT00074165

Purpose

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.

Condition	Intervention	Phase
Brain and Central Nervous System Tumors Drug/Agent Toxicity by Tissue/Organ Lymphoma Thrombocytopenia	Drug: Rituxan Drug: Cyclophosphamide Drug: Etoposide Drug: Etoposide phosphate Drug: Carboplatin Drug: Sodium thiosulfate Drug: Neupogen Drug: Neulasta Drug: Cytarabine	Phase II

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 II Trial Involving Patients With Recurrent PCNSL Treated With Carboplatin/BBBD, by Adding Rituxan (Rituximab), An Anti CD-20 Antibody, To The Treatment Regimen

Resource links provided by NLM:

Genetics Home Reference related topics: MYH9-related disorder

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Cyclophosphamide Cytarabine hydrochloride Sodium thiosulfate Etoposide Carboplatin Etoposide phosphate Filgrastim Granulocyte colony-stimulating factor Rituximab Pegfilgrastim Cytarabine Sodium hyposulfite

U.S. FDA Resources

Further study details as provided by OHSU Knight Cancer Institute:

Primary Outcome Measures:

Number of Participants With a Complete Response Rate to Chemotherapy Regimen Assessed by Radiographic Response at 2 Years. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Per RECIST criteria (v1.1) and assessed by magnetic resonance imaging (MRI): Complete response (CR), Disappearance of all target lesions.

Secondary Outcome Measures:

Number of Participants With Overall Survival Assessed by Clinical and Radiographic Response [ Time Frame: 5 years ] [ Designated as safety issue: No ]
Overall survival is measured from entry onto study until death from any cause or until death or progression of disease, respectively.
Progression-free Survival Assessed by Clinical and Radiographic Response From First Day of Treatment Until Tumor Progression [ Time Frame: 5 years ] [ Designated as safety issue: No ]
Quality of Life Assessed by EORTC QOL Before Treatment and Then Every 3 Months [ Time Frame: 5 years ] [ Designated as safety issue: No ]
Ototoxicity Assessed by Audiology Hearing Test Done Monthly During Treatment [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Effect of Sodium Thiosulfate (STS) on Granulocytes and Erythrocytes Assessed by Complete Blood Count Lab Values Done Weekly During Treatment [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment:	17
Study Start Date:	January 2003
Study Completion Date:	December 2010
Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: All subjects	Drug: Rituxan Total dose: 375mg/m2 infused IV; Every 4 weeks for up to one year. Other Name: Rituximab Drug: Cyclophosphamide Dose 330mg/m2 x 2 days infused IV; Every 4 weeks for up to 1 year Drug: Etoposide Dose 200mg/m2 x 2 days infused IV; Every 4 weeks for up to one year. Etoposide phosphate may be given instead. Drug: Etoposide phosphate Dose 200mg/m2 infused IV x 2 days; Every 4 weeks for up to one year. Etoposide may be given instead. Drug: Carboplatin Dose: 200mg/m2 x 2 days infused IA with BBBD; 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 Infused IV x 2 days Other Name: STS Drug: Neupogen 48 hours after chemotherapy, QD x 7-10 days until WBC greater than 5000. 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: Cytarabine Dose: 40mg on Day 14 following chemotherapy

Arms

Assigned Interventions

Experimental: All subjects

Drug: Rituxan

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

Other Name: Rituximab

Drug: Cyclophosphamide

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

Drug: Etoposide

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

Drug: Etoposide phosphate

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

Drug: Carboplatin

Dose: 200mg/m2 x 2 days infused IA with BBBD; 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

Infused IV x 2 days

Other Name: STS

Drug: Neupogen

48 hours after chemotherapy, QD x 7-10 days until WBC greater than 5000. 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: Cytarabine

Dose: 40mg on Day 14 following chemotherapy

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.

Eligibility

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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00074165

Locations

United States, Ohio
Good Samaritan Hospital Cancer Treatment Center, Hatton Institute
Cincinnati, Ohio, United States, 45220
United States, Oregon
Knight Cancer Institute at Oregon Health and Science University
Portland, Oregon, United States, 97239-3098

Sponsors and Collaborators

OHSU Knight Cancer Institute

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Edward A. Neuwelt, MD

OHSU Knight Cancer Institute

More Information

No publications provided

Responsible Party:	OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:	NCT00074165 History of Changes
Other Study ID Numbers:	OHSU-641, 5R01CA137488-15, ONC-02059-LX, 641, 7465
Study First Received:	December 10, 2003
Results First Received:	October 10, 2011
Last Updated:	November 21, 2011
Health Authority:	United States: Institutional Review Board

Keywords provided by OHSU Knight Cancer Institute:

drug/agent toxicity by tissue/organ
thrombocytopenia
intraocular lymphoma
primary central nervous system non-Hodgkin lymphoma
primary central nervous system Hodgkin lymphoma

Additional relevant MeSH terms:

Lymphoma
Nervous System Neoplasms
Thrombocytopenia
Central Nervous System Neoplasms
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms by Site
Nervous System Diseases
Blood Platelet Disorders
Hematologic Diseases
Cyclophosphamide

Cytarabine
Rituximab
Etoposide phosphate
Etoposide
Carboplatin
Sodium thiosulfate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 09, 2012