Lymphoma, Follicular
Conditions
Brief summary
This study will evaluate the efficacy, safety, and tolerability of long-term maintenance therapy with rituximab in participants with advanced follicular lymphoma who have had a positive response to first-line treatment with a rituximab-containing regimen. The anticipated time on study treatment is 2 years, and the target sample size is 124 individuals.
Interventions
DRUGRituximab
Rituximab will be administered at 375 mg/m\^2 every 8 weeks for 24 months or until progression, relapse, death, or institution of a new anti-lymphoma treatment.
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 greater than (\>) 18 years of age * Histologically confirmed follicular lymphoma Grade 1, 2, or 3a with lymph node biopsy within 4 months of induction treatment * No previous anti-lymphoma treatment before induction chemotherapy (first-line-treated participants only are eligible) * Verified complete or partial remission after first-line induction therapy including rituximab
Exclusion criteria
* Grade 3b follicular lymphoma * Transformation to high-grade lymphoma (except to Grade 3a) of previously existing follicular lymphoma * Presence of central nervous system lymphoma * Acquired immunodeficiency syndrome-related lymphoma * Other primary malignancy (other than squamous cell cancer of the skin or in situ cancer of the cervix) for which the participant has not been disease-free for greater than or equal to (\>=) 5 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event-free Survival | From randomization to the time to progression, relapse, death from any cause, or institution of a new treatment, whichever occurs first, assessed up to 5 years | Event-free survival (EFS) was defined as the time from baseline (Week 0) to the time to progression, relapse, death from any cause, or institution of a new treatment, whichever occurs first. Mean EFS was estimated by the Kaplan-Meier estimation and provided with their 95% confidence interval. ITT population (patients who received at least one maintenance MabThera infusion) was used for this analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From randomization until death, assessed up to 5 years | Overall survival, defined as the time between baseline (Week 0) and the date of death irrespective of the cause of death. Mean OS was estimated by the Kaplan-Meier estimation and provided with their 95% confidence interval. ITT population was used for this analysis. |
| Time to Progression (TTP) | From baseline (Week 0) to disease progression, relapse, death from the follicular lymphoma or institution of a new regimen, whichever occurs first, assessed up to 5 years | Time to progression (TTP) defined as time from baseline to disease progression or relapse, death from the follicular lymphoma or institution of a new regimen because of the follicular lymphoma. Mean TTP was estimated by the Kaplan-Meier estimation and provided with their 95% confidence interval. ITT population was used for this analysis. |
| Number of Participants With Adverse Events (AEs) | Up to 27 months | An adverse event (AE) was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. A serious adverse event (SAE) was defined as any untoward medical occurrence that is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, congenital anomaly/birth defect, requires intervention to prevent permanent impairment or damage, or results in death |
| Duration of Response (DR) | From first documented response to induction treatment to relapse or progression or death, assessed up to 5 years | Duration of Response (DR) defined as time from first documented response to induction treatment to relapse or progression or death from the follicular lymphoma. Mean DR was estimated by the Kaplan-Meier estimation and provided with their 95% confidence interval. |
| Disease-free Survival (DFS) | From first documented complete response to induction treatment to relapse or progression or death, whichever occurs first, assessed up to 5 years | Disease free survival (DFS) being defined as time from first documented complete response to induction treatment to relapse or progression or death from the follicular lymphoma. Mean DFS was estimated by the Kaplan-Meier estimation and provided with their 95% confidence interval. |
| Time to Next Anti-lymphoma Treatment (TTNLT) | From baseline (Week 0) to institution of a new antilymphoma regimen, assessed up to 5 years | Time to next anti-lymphoma treatment (TTNLT) defined as time from baseline to institution of a new antilymphoma regimen (including chemo-, radio- or immunotherapies). Mean TTNLT was estimated by the Kaplan-Meier estimation and provided with their 95% confidence interval. |
Countries
Hungary
Participant flow
Recruitment details
This study was conducted between 08 July 2005 to 12 Aug 2013 at 15 sites in Hungary.
Pre-assignment details
A total number of 124 patients were recruited. Of these, 83 patients completed the maintenance therapy with rituximab (MabThera) and entered the 3-year follow-up phase. Of these, 69 patients completed the follow-up phase.
Participants by arm
| Arm | Count |
|---|---|
| Rituximab Participants received rituximab 375 milligrams per meter square (mg/m\^2) every 8 weeks for 24 months | 124 |
| Total | 124 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 6 |
| Overall Study | Complete remission | 7 |
| Overall Study | Lost to Follow-up | 5 |
| Overall Study | New anti-lymphoma treatment | 1 |
| Overall Study | Non-compliance | 9 |
| Overall Study | Physician Decision | 3 |
| Overall Study | Progression of the disease | 18 |
| Overall Study | Unknown reason | 1 |
| Overall Study | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | Rituximab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 22 Participants |
| Age, Categorical Between 18 and 65 years | 102 Participants |
| Age, Continuous | 53 years |
| Sex: Female, Male Female | 84 Participants |
| Sex: Female, Male Male | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 3 / 124 |
| serious Total, serious adverse events | 14 / 124 |
Outcome results
Primary
Event-free Survival
Event-free survival (EFS) was defined as the time from baseline (Week 0) to the time to progression, relapse, death from any cause, or institution of a new treatment, whichever occurs first. Mean EFS was estimated by the Kaplan-Meier estimation and provided with their 95% confidence interval. ITT population (patients who received at least one maintenance MabThera infusion) was used for this analysis.
Time frame: From randomization to the time to progression, relapse, death from any cause, or institution of a new treatment, whichever occurs first, assessed up to 5 years
Population: ITT population: All participants who received at least one maintenance rituximab infusion were included in the analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Rituximab | Event-free Survival | 53.944 months |
Secondary
Disease-free Survival (DFS)
Disease free survival (DFS) being defined as time from first documented complete response to induction treatment to relapse or progression or death from the follicular lymphoma. Mean DFS was estimated by the Kaplan-Meier estimation and provided with their 95% confidence interval.
Time frame: From first documented complete response to induction treatment to relapse or progression or death, whichever occurs first, assessed up to 5 years
Population: ITT population: All participants who received at least one maintenance rituximab infusion were included in the analysis. Subset of the ITT population was used since not the entire ITT population provided appropriate data for analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Rituximab | Disease-free Survival (DFS) | 66.737 months |
Secondary
Duration of Response (DR)
Duration of Response (DR) defined as time from first documented response to induction treatment to relapse or progression or death from the follicular lymphoma. Mean DR was estimated by the Kaplan-Meier estimation and provided with their 95% confidence interval.
Time frame: From first documented response to induction treatment to relapse or progression or death, assessed up to 5 years
Population: ITT population: All participants who received at least one maintenance rituximab infusion were included in the analysis. Subset of the ITT population was used since not the entire ITT population provided appropriate data for analysis
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Rituximab | Duration of Response (DR) | 63.159 months |
Secondary
Number of Participants With Adverse Events (AEs)
An adverse event (AE) was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. A serious adverse event (SAE) was defined as any untoward medical occurrence that is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, congenital anomaly/birth defect, requires intervention to prevent permanent impairment or damage, or results in death
Time frame: Up to 27 months
Population: Safety population: All participants who received at least one dose of study medication and had safety data after the first dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab | Number of Participants With Adverse Events (AEs) | SAEs | 14 participants |
| Rituximab | Number of Participants With Adverse Events (AEs) | Non serious AEs | 32 participants |
Secondary
Overall Survival (OS)
Overall survival, defined as the time between baseline (Week 0) and the date of death irrespective of the cause of death. Mean OS was estimated by the Kaplan-Meier estimation and provided with their 95% confidence interval. ITT population was used for this analysis.
Time frame: From randomization until death, assessed up to 5 years
Population: ITT population: All participants who received at least one maintenance rituximab infusion were included in the analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Rituximab | Overall Survival (OS) | 72.959 months |
Secondary
Time to Next Anti-lymphoma Treatment (TTNLT)
Time to next anti-lymphoma treatment (TTNLT) defined as time from baseline to institution of a new antilymphoma regimen (including chemo-, radio- or immunotherapies). Mean TTNLT was estimated by the Kaplan-Meier estimation and provided with their 95% confidence interval.
Time frame: From baseline (Week 0) to institution of a new antilymphoma regimen, assessed up to 5 years
Population: ITT population: All participants who received at least one maintenance rituximab infusion were included in the analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Rituximab | Time to Next Anti-lymphoma Treatment (TTNLT) | 59.236 months |
Secondary
Time to Progression (TTP)
Time to progression (TTP) defined as time from baseline to disease progression or relapse, death from the follicular lymphoma or institution of a new regimen because of the follicular lymphoma. Mean TTP was estimated by the Kaplan-Meier estimation and provided with their 95% confidence interval. ITT population was used for this analysis.
Time frame: From baseline (Week 0) to disease progression, relapse, death from the follicular lymphoma or institution of a new regimen, whichever occurs first, assessed up to 5 years
Population: ITT population: All participants who received at least one maintenance rituximab infusion were included in the analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Rituximab | Time to Progression (TTP) | 56.024 months |