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Study was terminated early due to lack of enrollment.
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This study will evaluate the efficacy and safety of MabThera plus high dose methotrexate plus high dose cytarabine in patients with central nervous system non-Hodgkin's lymphoma. Eligible patients will receive a treatment regimen consisting of MabThera (750mg/m2 iv) plus methotrexate (8g/m2 iv) given at intervals up to week 22, plus cytarabine (2g/m2 iv) at week 11 and week 22. The anticipated time on study treatment is 3-12 months, and the target sample size is <100 individuals.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| rituximab [MabThera/Rituxan] | Drug | 750mg/m2 iv |
| |
| Methotrexate |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With a Complete Response (CR) or Unconfirmed CR (CRu) | CR: complete disappearance of all enhancing abnormalities on contrast-enhanced cranial magnetic resonance imaging (MRI); no evidence of active ocular lymphoma as defined by absence of cells in the vitreous and resolution of any previously documented retinal or optic nerve infiltrates; negative cerebrospinal fluid (CSF) cytology; at the time of CR determination, participant had discontinued use of all corticosteroids for at least 2 weeks. CRu requires fulfillment of CR criteria but with these limitations: Fulfills CR criteria but had continued requirement for corticosteroid therapy at any dose; small but persistent enhancing abnormality on MRI related to biopsy or focal hemorrhage; persistent minor abnormality on follow-up ophthalmologic exam (related to persistent non-malignant cells in vitreous, or alterations in retina/optic nerve not consistent with tumor infiltration) if the abnormality is unlikely to represent ocular lymphoma. | Week 24 |
| Percentage of Participants With a CR, CRu or Partial Response (PR) | PR: greater than or equal to (≥) 50 percent (%) decrease in the contrast-enhancing lesion seen on MRI as compared with the baseline images; (2) Corticosteroid dose was irrelevant to the determination of PR; for participants with ocular disease, ophthalmologic exam must show a decrease in vitreous cell count or retina/optic nerve cellular infiltrate but may have continued to show persistent malignant or suspicious cells; for participants with CSF positive for neoplastic cells, CSF cytology may be negative or continue to show persistent malignant or suspicious cells in patients with ≥50% decrease in the primary brain lesions; no new sites of disease. | Week 24 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Initial CR or CRu and Subsequent Disease Relapse | Week 24 | |
| Overall Survival | Time from entry into trial until death of any cause. Participants who were alive at the time of the analysis were censored at the date of the last follow-up assessment. Participants without follow-up assessment were censored at the day of last dose and participants with no post baseline information were censored at the baseline date. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Greenfield Park | Quebec | J4V 2H1 | Canada | |||
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| ID | Title | Description |
|---|---|---|
| FG000 | Rituximab, Cytarabine, and Methotrexate (MTX) | Participants received single doses of rituximab 750 milligrams per square meter (mg/m^2) intravenously (IV) at Weeks 1 through 5, and 7, 9, 11, 14, 16, 18, 20, and 22; cytarabine 2 grams per square meter (g/m^2) IV every 24 hours for 2 doses at Weeks 11 and 22; and single doses of MTX 8 g/m^2 IV at Weeks 3, 5, 7, 9, 14, 16, 18, and 20. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Safety population: all participants who received any amount of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Rituximab, Cytarabine, and MTX | Participants received single doses of rituximab 750 mg/m^2 IV at Weeks 1 through 5, and 7, 9, 11, 14, 16, 18, 20, and 22; cytarabine 2 g/m^2 IV every 24 hours for 2 doses at Weeks 11 and 22; and single doses of MTX 8 g/m^2 IV at Weeks 3, 5, 7, 9, 14, 16, 18, and 20. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Percentage of Participants With a Complete Response (CR) or Unconfirmed CR (CRu) | CR: complete disappearance of all enhancing abnormalities on contrast-enhanced cranial magnetic resonance imaging (MRI); no evidence of active ocular lymphoma as defined by absence of cells in the vitreous and resolution of any previously documented retinal or optic nerve infiltrates; negative cerebrospinal fluid (CSF) cytology; at the time of CR determination, participant had discontinued use of all corticosteroids for at least 2 weeks. CRu requires fulfillment of CR criteria but with these limitations: Fulfills CR criteria but had continued requirement for corticosteroid therapy at any dose; small but persistent enhancing abnormality on MRI related to biopsy or focal hemorrhage; persistent minor abnormality on follow-up ophthalmologic exam (related to persistent non-malignant cells in vitreous, or alterations in retina/optic nerve not consistent with tumor infiltration) if the abnormality is unlikely to represent ocular lymphoma. | Due to early study termination, all efficacy data were documented by data listings only, no data analysis was performed. | Posted | Week 24 |
|
Baseline up to 24 weeks.
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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, Cytarabine, and MTX | Participants received single doses of rituximab 750 mg/m^2 IV at Weeks 1 through 5, and 7, 9, 11, 14, 16, 18, 20, and 22; cytarabine 2 g/m^2 IV every 24 hours for 2 doses at Weeks 11 and 22; and single doses of MTX 8 g/m^2 IV at Weeks 3, 5, 7, 9, 14, 16, 18, and 20. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (9.0) | Non-systematic Assessment |
The study was terminated early due to lack of enrollment.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications | Hoffmann-LaRoche | 800-821-8590 | genentech@druginfo.com |
Not provided
| ID | Term |
|---|---|
| D008223 | Lymphoma |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
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| ID | Term |
|---|---|
| D000069283 | Rituximab |
| D008727 | Methotrexate |
| D003561 | Cytarabine |
| ID | Term |
|---|---|
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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| Drug |
8g/m2 iv |
|
| Cytarabine | Drug | 2g/m2 iv |
|
| Time of last follow-up assessment between Day 1 and 3 years |
| Progression-Free Survival (PFS) | PFS was defined as the time interval between the entry into trial and occurrence of one of the following events: progression of disease (PD) or death as a result of primary central nervous system lymphoma (PCNSL). Participants who were withdrawn from the study without documented progression and for whom there existed case report form (CRF) evidence that evaluations had been made, were censored at the date of last tumor assessment when participant was known to be progression free. Participants without postbaseline tumor assessments but known to be alive were censored at the time of randomization. PD required a ≥25% increase in the contrast-enhanced lesion seen on MRI as compared with baseline or best response (comparison should be made to the smallest of multiple lesions); progression of ocular disease as indicated by an increase in vitreous cell count or progressive retinal or optic nerve infiltration, appearance of any new lesion or site of disease during or at the end of therapy. | Week 24 |
| Québec |
| Quebec |
| G1J 1Z4 |
| Canada |
| Study terminated by Sponsor |
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Title |
|---|
| Description |
|---|
| OG000 | Rituximab, Cytarabine, and MTX | Participants received single doses of rituximab 750 mg/m^2 IV at Weeks 1 through 5, and 7, 9, 11, 14, 16, 18, 20, and 22; cytarabine 2 g/m^2 IV every 24 hours for 2 doses at Weeks 11 and 22; and single doses of MTX 8 g/m^2 IV at Weeks 3, 5, 7, 9, 14, 16, 18, and 20. |
|
| Primary | Percentage of Participants With a CR, CRu or Partial Response (PR) | PR: greater than or equal to (≥) 50 percent (%) decrease in the contrast-enhancing lesion seen on MRI as compared with the baseline images; (2) Corticosteroid dose was irrelevant to the determination of PR; for participants with ocular disease, ophthalmologic exam must show a decrease in vitreous cell count or retina/optic nerve cellular infiltrate but may have continued to show persistent malignant or suspicious cells; for participants with CSF positive for neoplastic cells, CSF cytology may be negative or continue to show persistent malignant or suspicious cells in patients with ≥50% decrease in the primary brain lesions; no new sites of disease. | Due to early study termination, all efficacy data were documented by data listings only, no data analysis was performed. | Posted | Week 24 |
|
|
| Secondary | Percentage of Participants With Initial CR or CRu and Subsequent Disease Relapse | Due to early study termination, all efficacy data were documented by data listings only, no data analysis was performed. | Posted | Week 24 |
|
|
| Secondary | Overall Survival | Time from entry into trial until death of any cause. Participants who were alive at the time of the analysis were censored at the date of the last follow-up assessment. Participants without follow-up assessment were censored at the day of last dose and participants with no post baseline information were censored at the baseline date. | Due to early study termination, all efficacy data were documented by data listings only, no data analysis was performed. | Posted | Time of last follow-up assessment between Day 1 and 3 years |
|
|
| Secondary | Progression-Free Survival (PFS) | PFS was defined as the time interval between the entry into trial and occurrence of one of the following events: progression of disease (PD) or death as a result of primary central nervous system lymphoma (PCNSL). Participants who were withdrawn from the study without documented progression and for whom there existed case report form (CRF) evidence that evaluations had been made, were censored at the date of last tumor assessment when participant was known to be progression free. Participants without postbaseline tumor assessments but known to be alive were censored at the time of randomization. PD required a ≥25% increase in the contrast-enhanced lesion seen on MRI as compared with baseline or best response (comparison should be made to the smallest of multiple lesions); progression of ocular disease as indicated by an increase in vitreous cell count or progressive retinal or optic nerve infiltration, appearance of any new lesion or site of disease during or at the end of therapy. | Due to early study termination, all efficacy data were documented by data listings only, no data analysis was performed. | Posted | Week 24 |
|
|
| 0 |
| 5 |
| 5 |
| 5 |
| Leukopenia | Blood and lymphatic system disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Eye allergy | Eye disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Gingival pain | Gastrointestinal disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Generalised oedema | General disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Hyperthermia | General disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Injection site erythema | General disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Injection site pain | General disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Non-cardiac chest pain | General disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Pain | General disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Vessel puncture site bruise | General disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Hepatitis | Hepatobiliary disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Conjunctivitis bacterial | Infections and infestations | MedDRA (9.0) | Non-systematic Assessment |
|
| Herpes zoster | Infections and infestations | MedDRA (9.0) | Non-systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (9.0) | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (9.0) | Non-systematic Assessment |
|
| Drug toxicity | Injury, poisoning and procedural complications | MedDRA (9.0) | Non-systematic Assessment |
|
| Skin laceration | Injury, poisoning and procedural complications | MedDRA (9.0) | Non-systematic Assessment |
|
| Wound | Injury, poisoning and procedural complications | MedDRA (9.0) | Non-systematic Assessment |
|
| Creatinine renal clearance decreased | Investigations | MedDRA (9.0) | Non-systematic Assessment |
|
| Hepatic enzyme abnormal | Investigations | MedDRA (9.0) | Non-systematic Assessment |
|
| Hepatic enzyme increased | Investigations | MedDRA (9.0) | Non-systematic Assessment |
|
| Weight increased | Investigations | MedDRA (9.0) | Non-systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Electrolyte imbalance | Metabolism and nutrition disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Hypernatraemia | Metabolism and nutrition disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Malnutrition | Metabolism and nutrition disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Mobility decreased | Musculoskeletal and connective tissue disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Dementia | Nervous system disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Loss of consciousness | Nervous system disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Neurological symptom | Nervous system disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Agitation | Psychiatric disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Confusional state | Psychiatric disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Mood altered | Psychiatric disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Renal cyst | Renal and urinary disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Renal failure | Renal and urinary disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Urinary incontinence | Renal and urinary disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Urinary retention | Renal and urinary disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Erectile dysfunction | Reproductive system and breast disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Pharyngolaryngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Rales | Respiratory, thoracic and mediastinal disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Respiratory distress | Respiratory, thoracic and mediastinal disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Upper respiratory tract congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Skin burning sensation | Skin and subcutaneous tissue disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Arterial thrombosis limb | Vascular disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (9.0) | Non-systematic Assessment |
|
| Venous thrombosis limb | Vascular disorders | MedDRA (9.0) | Non-systematic Assessment |
|
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D000630 | Aminopterin |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D001087 | Arabinonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |