| ID | Type | Description | Link |
|---|---|---|---|
| 5R01CA137488-15 | U.S. NIH Grant/Contract | View source | |
| ONC-02059-LX | Other Identifier | OHSU Knight Cancer Institute | |
| 641 | Other Identifier | OHSU eIRB | |
| 7465 | Other Identifier | OHSU IRB (discontinued number) | |
| OHSU-641 | Other Identifier | OHSU IRB |
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Lack of accrual
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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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.
OBJECTIVES:
Primary
Secondary
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| All subjects | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rituxan | Drug | Total dose: 375mg/m2 infused IV; Every 4 weeks for up to one year. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With a Complete Response Rate to Chemotherapy Regimen Assessed by Radiographic Response at 2 Years. | Per RECIST criteria (v1.1) and assessed by magnetic resonance imaging (MRI): Complete response (CR), Disappearance of all target lesions. | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Overall Survival Assessed by Clinical and Radiographic Response | Overall survival is measured from entry onto study until death from any cause or until death or progression of disease, respectively. | 5 years |
| Progression-free Survival Assessed by Clinical and Radiographic Response From First Day of Treatment Until Tumor Progression |
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INCLUSION CRITERIA:
EXCLUSION CRITERIA:
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| Name | Affiliation | Role |
|---|---|---|
| Edward A. Neuwelt, MD | OHSU Knight Cancer Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Good Samaritan Hospital Cancer Treatment Center, Hatton Institute | Cincinnati | Ohio | 45220 | United States | ||
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| ID | Title | Description |
|---|---|---|
| FG000 | Rituximab and Carboplatin | Rituximab: (i.v.) 375 mg/m^2 given the evening before blood brain barrier disruption(BBBD) procedure day 1 Carboplatin: (i.a.) 200 mg/m^2 /day x 2 days = 400 mg/m^2 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Cyclophosphamide | Drug | Dose 330mg/m2 x 2 days infused IV; Every 4 weeks for up to 1 year |
|
| Etoposide | 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 | Drug | Dose 200mg/m2 infused IV x 2 days; Every 4 weeks for up to one year. Etoposide may be given instead. |
|
| Carboplatin | Drug | Dose: 200mg/m2 x 2 days infused IA with BBBD; Every 4 weeks for up to one year. |
|
| Sodium thiosulfate | Drug | Dose: 4 hrs post carboplatin = 20gm/m2; Dose: 8 hrs post carboplatin = 16gm/m2 Infused IV x 2 days |
|
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| Neupogen | Drug | 48 hours after chemotherapy, QD x 7-10 days until WBC greater than 5000. Neulasta (Pegfilgrastim) may be given instead. |
|
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| Neulasta | Drug | Dose: 6mg, 24-72 hours after chemotherapy. Neupogen may be given instead. |
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| Cytarabine | Drug | Dose: 40mg on Day 14 following chemotherapy |
|
| 5 years |
| Quality of Life Assessed by EORTC QOL Before Treatment and Then Every 3 Months | 5 years |
| Ototoxicity Assessed by Audiology Hearing Test Done Monthly During Treatment | 2 years |
| Effect of Sodium Thiosulfate (STS) on Granulocytes and Erythrocytes Assessed by Complete Blood Count Lab Values Done Weekly During Treatment | 2 years |
| Knight Cancer Institute at Oregon Health and Science University |
| Portland |
| Oregon |
| 97239-3098 |
| United States |
| COMPLETED |
|
| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Rituximab and Carboplatin | Rituximab: (i.v.) 375 mg/m^2 given the evening before blood brain barrier disruption(BBBD) procedure day 1 Carboplatin: (i.a.) 200 mg/m^2 /day x 2 days = 400 mg/m^2 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With a Complete Response Rate to Chemotherapy Regimen Assessed by Radiographic Response at 2 Years. | Per RECIST criteria (v1.1) and assessed by magnetic resonance imaging (MRI): Complete response (CR), Disappearance of all target lesions. | Posted | Number | Participants | 2 years |
|
|
| |||||||||||||||||||||||||||
| Secondary | Number of Participants With Overall Survival Assessed by Clinical and Radiographic Response | Overall survival is measured from entry onto study until death from any cause or until death or progression of disease, respectively. | Data not collected due to low accrual and early termination. | Posted | 5 years |
|
| |||||||||||||||||||||||||||||
| Secondary | Progression-free Survival Assessed by Clinical and Radiographic Response From First Day of Treatment Until Tumor Progression | Data not collected due to low accrual and early termination. | Posted | 5 years |
|
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| Secondary | Quality of Life Assessed by EORTC QOL Before Treatment and Then Every 3 Months | Data not collected due to low accrual and early termination. | Posted | 5 years |
|
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| Secondary | Ototoxicity Assessed by Audiology Hearing Test Done Monthly During Treatment | Data not collected due to low accrual and early termination. | Posted | 2 years |
|
| ||||||||||||||||||||||||||||||
| Secondary | Effect of Sodium Thiosulfate (STS) on Granulocytes and Erythrocytes Assessed by Complete Blood Count Lab Values Done Weekly During Treatment | Data not collected due to low accrual and early termination. | Posted | 2 years |
|
|
During study treatment (1 year).
Unanticipated Problems (UP) and Adverse Events (AE) were reported to IRB according to OHSU's (coordinating center) policies, procedures and guidelines posted on the OHSU IRB web site. NCI Common Toxicity Criteria used to assess AEs.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Rituximab and Carboplatin | Rituximab: (i.v.) 375 mg/m^2 given the evening before blood brain barrier disruption(BBBD) procedure day 1 Carboplatin: (i.a.) 200 mg/m^2 /day x 2 days = 400 mg/m^2 | 0 | 17 | 16 | 17 | 1 | 17 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenic Fever | Blood and lymphatic system disorders |
| |||
| Unresponsiveness | General disorders | Hospitalized for unresponsiveness |
| ||
| Anemia | Blood and lymphatic system disorders |
| |||
| Superficial Epidermolysis | Musculoskeletal and connective tissue disorders |
| |||
| Neurological Symptoms | Psychiatric disorders |
| |||
| Stroke | Vascular disorders |
| |||
| Chemical Meningitis and Seizures | Vascular disorders |
| |||
| Extended Hospitalization | Investigations |
| |||
| Hospitalized for Fall | Injury, poisoning and procedural complications |
| |||
| Death | General disorders |
| |||
| Carotid Artery Tear | Blood and lymphatic system disorders |
| |||
| Electrolyte Imbalance and Increased Blood Sodium | Blood and lymphatic system disorders |
| |||
| Bronchitis | Respiratory, thoracic and mediastinal disorders |
| |||
| Atrial Fibrillation | Cardiac disorders |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leg Pain | General disorders |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Edward Neuwelt | OHSU Knight Cancer Institute | 503-494-5626 | neuwelte@ohsu.edu |
| ID | Term |
|---|---|
| D016543 | Central Nervous System Neoplasms |
| D064420 | Drug-Related Side Effects and Adverse Reactions |
| D008223 | Lymphoma |
| D013921 | Thrombocytopenia |
| D064090 | Intraocular Lymphoma |
| ID | Term |
|---|---|
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D009422 | Nervous System Diseases |
| D064419 | Chemically-Induced Disorders |
| D009370 | Neoplasms by Histologic Type |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D001791 | Blood Platelet Disorders |
| D006402 | Hematologic Diseases |
| D000095542 | Cytopenia |
| D005134 | Eye Neoplasms |
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| ID | Term |
|---|---|
| D000069283 | Rituximab |
| D003520 | Cyclophosphamide |
| D005047 | Etoposide |
| C061400 | etoposide phosphate |
| D016190 | Carboplatin |
| C017717 | sodium thiosulfate |
| D000069585 | Filgrastim |
| D016179 | Granulocyte Colony-Stimulating Factor |
| C455861 | pegfilgrastim |
| D003561 | Cytarabine |
| ID | Term |
|---|---|
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D011034 | Podophyllotoxin |
| D013764 | Tetrahydronaphthalenes |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D011083 | Polycyclic Compounds |
| D005960 | Glucosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D056831 | Coordination Complexes |
| D003115 | Colony-Stimulating Factors |
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D016298 | Hematopoietic Cell Growth Factors |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D001685 | Biological Factors |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001087 | Arabinonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
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