Diffuse Large B-Cell Lymphoma
Conditions
Brief summary
This multicenter, open-label study will assess the efficacy and safety of MabThera (rituximab) added to standard chemotherapy in participants with untreated Mantle Cell Lymphoma not eligible for autologous stem cell transplantation. Participants will receive MabThera (372 mg/m\^2 intravenously) on Day 1 of each 28-day treatment cycle in addition to standard chemotherapy for 6 cycles. In participants experiencing complete or partial response, MabThera will be continued as consolidation therapy for 2 more cycles.
Interventions
DRUGCyclophosphamide
as prescribed, 6 cycles
DRUGFludarabine
as prescribed, 6 cycles
DRUGMitoxantrone
as prescribed, 6 cycles
DRUGRituximab
375 mg/m\^2 intravenously, Day 1 of each 28-day cycle, up to 8 cycles
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
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 participants, \>/=18 years of age * untreated Mantle Cell Lymphoma, not eligible for Autologous Stem Cell Transplantation * known mantle cell lymphoma international prognostic index (MIPI) at diagnosis * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * adequate hematological, renal and hepatic function
Exclusion criteria
* known hypersensitivity to murine proteins or chemotherapy regimen * previous first-line therapy * history of other malignancy within the last 5 years, except for squamous cell carcinoma, basal cell carcinoma of the skin or in situ cervical carcinoma * active infection * clinically significant cardiac disease * regular corticosteroid treatment in the 4 weeks prior to first dose of study drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | Up to 50 months (approximately) | Overall Response Rate (ORR) was determined by tumor response according to International Workshop Group to Standardize Response Criteria for mantle cell lymphoma (MCL) criteria from confirmed evaluations of both target, radiographically evaluated, and non-target lesions. A responder is defined as a subject experiencing either a complete (CR)/ unconfirmed complete (Cru), or partial response (PR) by these criteria. As per criteria; CR = disappearance of all evidence of disease; CRu = the sum of the product of the diameters (SPD) of multiple nodes decreased by at least 75%; PR = regression of measurable disease and no new sites. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From the time of enrollment until death due to any cause (up to 50 months [approximately]) | Overall survival is defined as time from date of enrollment to the date of death, regardless of the cause of death. |
| Progression-free Survival (PFS) | From the time of enrollment until death due to any cause (up to 50 months [approximately]) | PFS is defined as the interval between the day of enrollment and the first documentation of progressive disease or death. Progression of disease is defined as at least a 20 percent (%) increase in the sum of longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. |
| Number of Participant With Adverse Event (AE) | Up to 50 months (approximately) | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with study treatment. |
Countries
Romania
Participant flow
Pre-assignment details
A total 8 participants were enrolled from Romania.
Participants by arm
| Arm | Count |
|---|---|
| Rituximab Rituximab, 375 milligram per meter square (mg/m\^2) was given intravenously on Day 1 and then every 28 days (+/-7 days) for 6 cycles, followed by 2 consolidated infusions in responders as rituximab induction therapy. Rituximab infusions were administered concomitantly with regularly prescribed chemotherapy i.e., fludarabine, cyclophosphamide and mitoxantrone (maximum 6 cycles).
Cyclophosphamide: as prescribed, 6 cycles
Fludarabine: as prescribed, 6 cycles
Mitoxantrone: as prescribed, 6 cycles
Rituximab \[Mabthera/Rituxan\]: 375 mg/m\^2 intravenously, Day 1 of each 28-day cycle, up to 8 cycles | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 1 |
| Overall Study | Lost to Follow-up | 3 |
Baseline characteristics
| Characteristic | Rituximab |
|---|---|
| Age, Continuous | 60.50 years STANDARD_DEVIATION 7.964 |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 8 / 8 |
| serious Total, serious adverse events | 3 / 8 |
Outcome results
Primary
Overall Response Rate (ORR)
Overall Response Rate (ORR) was determined by tumor response according to International Workshop Group to Standardize Response Criteria for mantle cell lymphoma (MCL) criteria from confirmed evaluations of both target, radiographically evaluated, and non-target lesions. A responder is defined as a subject experiencing either a complete (CR)/ unconfirmed complete (Cru), or partial response (PR) by these criteria. As per criteria; CR = disappearance of all evidence of disease; CRu = the sum of the product of the diameters (SPD) of multiple nodes decreased by at least 75%; PR = regression of measurable disease and no new sites.
Time frame: Up to 50 months (approximately)
Population: Efficacy population included all the participants who had received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab | Overall Response Rate (ORR) | 87.5 percentage of participants |
Secondary
Number of Participant With Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with study treatment.
Time frame: Up to 50 months (approximately)
Population: Safety population included all the participants who had received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab | Number of Participant With Adverse Event (AE) | 8 participants |
Secondary
Overall Survival (OS)
Overall survival is defined as time from date of enrollment to the date of death, regardless of the cause of death.
Time frame: From the time of enrollment until death due to any cause (up to 50 months [approximately])
Population: Efficacy population included all the participants who had received at least one dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rituximab | Overall Survival (OS) | 927 days |
Secondary
Progression-free Survival (PFS)
PFS is defined as the interval between the day of enrollment and the first documentation of progressive disease or death. Progression of disease is defined as at least a 20 percent (%) increase in the sum of longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions.
Time frame: From the time of enrollment until death due to any cause (up to 50 months [approximately])
Population: Efficacy population included all the participants who had received at least one dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rituximab | Progression-free Survival (PFS) | 653 days |