Trial Outcomes & Findings for A Study of MabThera (Rituximab) in Primary Central Nervous System Lymphoma. (NCT NCT00517699)
NCT ID: NCT00517699
Last Updated: 2014-08-08
Results Overview
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.
TERMINATED
PHASE2
5 participants
Week 24
2014-08-08
Participant Flow
Participant milestones
| Measure |
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.
|
|---|---|
|
Overall Study
STARTED
|
5
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
5
|
Reasons for withdrawal
| Measure |
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.
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
|
Overall Study
Lack of Efficacy
|
1
|
|
Overall Study
Administrative error
|
1
|
|
Overall Study
Study terminated by Sponsor
|
2
|
Baseline Characteristics
A Study of MabThera (Rituximab) in Primary Central Nervous System Lymphoma.
Baseline characteristics by cohort
| Measure |
Rituximab, Cytarabine, and MTX
n=5 Participants
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.
|
|---|---|
|
Age, Continuous
|
59.8 years
STANDARD_DEVIATION 8.23 • n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Week 24Population: Due to early study termination, all efficacy data were documented by data listings only, no data analysis was performed.
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.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Week 24Population: Due to early study termination, all efficacy data were documented by data listings only, no data analysis was performed.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Week 24Population: Due to early study termination, all efficacy data were documented by data listings only, no data analysis was performed.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Time of last follow-up assessment between Day 1 and 3 yearsPopulation: Due to early study termination, all efficacy data were documented by data listings only, no data analysis was performed.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Week 24Population: Due to early study termination, all efficacy data were documented by data listings only, no data analysis was performed.
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.
Outcome measures
Outcome data not reported
Adverse Events
Rituximab, Cytarabine, and MTX
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Rituximab, Cytarabine, and MTX
n=5 participants at risk
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.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Blood and lymphatic system disorders
Leukopenia
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Blood and lymphatic system disorders
Neutropenia
|
80.0%
4/5 • Baseline up to 24 weeks.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Eye disorders
Eye allergy
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Gastrointestinal disorders
Abdominal pain
|
40.0%
2/5 • Baseline up to 24 weeks.
|
|
Gastrointestinal disorders
Constipation
|
60.0%
3/5 • Baseline up to 24 weeks.
|
|
Gastrointestinal disorders
Diarrhoea
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Gastrointestinal disorders
Dyspepsia
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Gastrointestinal disorders
Gingival pain
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Gastrointestinal disorders
Nausea
|
60.0%
3/5 • Baseline up to 24 weeks.
|
|
Gastrointestinal disorders
Vomiting
|
40.0%
2/5 • Baseline up to 24 weeks.
|
|
General disorders
Fatigue
|
60.0%
3/5 • Baseline up to 24 weeks.
|
|
General disorders
Generalised oedema
|
40.0%
2/5 • Baseline up to 24 weeks.
|
|
General disorders
Hyperthermia
|
60.0%
3/5 • Baseline up to 24 weeks.
|
|
General disorders
Injection site erythema
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
General disorders
Injection site pain
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
General disorders
Non-cardiac chest pain
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
General disorders
Oedema peripheral
|
60.0%
3/5 • Baseline up to 24 weeks.
|
|
General disorders
Pain
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
General disorders
Vessel puncture site bruise
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Hepatobiliary disorders
Hepatitis
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Infections and infestations
Conjunctivitis bacterial
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Infections and infestations
Herpes zoster
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Infections and infestations
Upper respiratory tract infection
|
40.0%
2/5 • Baseline up to 24 weeks.
|
|
Infections and infestations
Urinary tract infection
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Injury, poisoning and procedural complications
Drug toxicity
|
60.0%
3/5 • Baseline up to 24 weeks.
|
|
Injury, poisoning and procedural complications
Skin laceration
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Injury, poisoning and procedural complications
Wound
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Investigations
Creatinine renal clearance decreased
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Investigations
Hepatic enzyme abnormal
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Investigations
Hepatic enzyme increased
|
40.0%
2/5 • Baseline up to 24 weeks.
|
|
Investigations
Weight increased
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Metabolism and nutrition disorders
Electrolyte imbalance
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Metabolism and nutrition disorders
Hypernatraemia
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
100.0%
5/5 • Baseline up to 24 weeks.
|
|
Metabolism and nutrition disorders
Malnutrition
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Musculoskeletal and connective tissue disorders
Mobility decreased
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Nervous system disorders
Dementia
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Nervous system disorders
Dysgeusia
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Nervous system disorders
Headache
|
60.0%
3/5 • Baseline up to 24 weeks.
|
|
Nervous system disorders
Loss of consciousness
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Nervous system disorders
Neurological symptom
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Nervous system disorders
Somnolence
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Psychiatric disorders
Agitation
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Psychiatric disorders
Anxiety
|
40.0%
2/5 • Baseline up to 24 weeks.
|
|
Psychiatric disorders
Confusional state
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Psychiatric disorders
Insomnia
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Psychiatric disorders
Mood altered
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Renal and urinary disorders
Renal cyst
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Renal and urinary disorders
Renal failure
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Renal and urinary disorders
Urinary incontinence
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Renal and urinary disorders
Urinary retention
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Reproductive system and breast disorders
Erectile dysfunction
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Respiratory, thoracic and mediastinal disorders
Rales
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract congestion
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Skin and subcutaneous tissue disorders
Erythema
|
40.0%
2/5 • Baseline up to 24 weeks.
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Skin and subcutaneous tissue disorders
Rash
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Skin and subcutaneous tissue disorders
Skin burning sensation
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Vascular disorders
Arterial thrombosis limb
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Vascular disorders
Flushing
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Vascular disorders
Hot flush
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Vascular disorders
Hypertension
|
40.0%
2/5 • Baseline up to 24 weeks.
|
|
Vascular disorders
Hypotension
|
20.0%
1/5 • Baseline up to 24 weeks.
|
|
Vascular disorders
Venous thrombosis limb
|
20.0%
1/5 • Baseline up to 24 weeks.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER