Lymphoma
Conditions
Brief summary
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.
Interventions
DRUGrituximab [MabThera/Rituxan]
750mg/m2 iv
DRUGMethotrexate
8g/m2 iv
DRUGCytarabine
2g/m2 iv
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* adult patients, 18-80 years of age; * histological diagnosis of primary central nervous system lymphoma; * B-cell proliferation verified by positive staining for CD20; * \>=1 measurable lesion.
Exclusion criteria
* prior chemotherapy, other than corticosteroids, \>=6 weeks before and after diagnosis or surgery; * history of prior cranial irradiation; * evidence of plurisystemic non-Hodgkin's lymphoma; * other active malignant disease (other than basal cell or squamous cell cancer of skin,or cancer in situ of cervix; * uncontrolled active infection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Complete Response (CR) or Unconfirmed CR (CRu) | Week 24 | 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. |
| Percentage of Participants With a CR, CRu or Partial Response (PR) | Week 24 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Initial CR or CRu and Subsequent Disease Relapse | Week 24 | — |
| Overall Survival | Time of last follow-up assessment between Day 1 and 3 years | 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. |
| Progression-Free Survival (PFS) | Week 24 | 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. |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 5 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Administrative error | 1 |
| Overall Study | Lack of Efficacy | 1 |
| Overall Study | Study terminated by Sponsor | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Rituximab, Cytarabine, and MTX |
|---|---|
| Age, Continuous | 59.8 years STANDARD_DEVIATION 8.23 |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 5 / 5 |
| serious Total, serious adverse events | 0 / 5 |
Outcome results
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.
Time frame: Week 24
Population: Due to early study termination, all efficacy data were documented by data listings only, no data analysis was performed.
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.
Time frame: Week 24
Population: Due to early study termination, all efficacy data were documented by data listings only, no data analysis was performed.
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.
Time frame: Time of last follow-up assessment between Day 1 and 3 years
Population: Due to early study termination, all efficacy data were documented by data listings only, no data analysis was performed.
Secondary
Percentage of Participants With Initial CR or CRu and Subsequent Disease Relapse
Time frame: Week 24
Population: Due to early study termination, all efficacy data were documented by data listings only, no data analysis was performed.
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.
Time frame: Week 24
Population: Due to early study termination, all efficacy data were documented by data listings only, no data analysis was performed.