Non-Hodgkin's Lymphoma
Conditions
Brief summary
This study will evaluate the efficacy and safety of MabThera in combination chemotherapy, followed by maintenance treatment with MabThera. The anticipated time on study treatment is 1-2 years, and the target sample size is \<100 individuals.
Interventions
DRUGrituximab
1
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 65 Years
Healthy volunteers
No
Inclusion criteria
* adult patients 18-65 years of age; * previously untreated indolent nonfollicular non-Hodgkin's lymphoma; * active disease; * \>=3 involved sites.
Exclusion criteria
* typical chronic lymphocytic leukemia; * other malignancies within 3 years before study, except basal or squamous cell skin cancer or cancer in situ of the cervix; * systemic corticosteroid use for \>1 month; * significant cardiovascular disease; * central nervous system involvement; * hepatitis B or C virus infection, or HIV infection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Remaining Failure-Free After 2 Years From Treatment Start Date | Month 28 | Percentage of participants who at 2 years from the start of treatment remained free from documented disease progression, relapse, or death. Failure status was based on tumor evaluation performed on Month 28. Participants who did not have a tumor evaluation at Month 28 were counted as failures. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving a Best Overall Response of CR, CRu, or PR by Study Phase | Baseline, Months 4, 7 (Induction Phase), 11, 16 (Maintenance Phase),22, 28, 34, and 40(Follow-Up Phase) | CR: complete disappearance of all symptoms/objective signs of disease (enlarged lymph nodes, hepatomegaly, splenomegaly) for at least 3 months following definitive re-evaluation at end of therapy. For initial bone marrow involvement, clearance of bone marrow documented by biopsy, normalization of blood counts with granulocytes greater than (\>)1,500 per microliter (/µL), hemoglobin \>12 grams per deciliter (g/dL), platelets \>100,000/µL. CRu: disappearance of all symptoms and nearly all measurable lesions, but persistence of some radiologic abnormalities with normalization of all biologic abnormalities; normalization of the performance status for at least 3 months after the definite evaluation of therapy. PR: at least 50 percent (%) reduction of measurable and evaluable lymphoma involvement for at least 4 weeks without occurrence of new manifestations, normalization of blood counts. Participants without evaluation at end of induction/maintenance phase were considered nonresponders. |
| Percentage of Participants Achieving a Response by Response Type and Study Phase | Baseline, Months 4, 7, 11, 16, 22, 28, 34, and 40 | CR: complete disappearance of all symptoms/objective signs of disease (enlarged lymph nodes, hepatomegaly, splenomegaly) for at least 3 months following definitive re-evaluation at end of therapy. For initial bone marrow involvement, clearance of bone marrow documented by biopsy, normalization of blood counts with granulocytes greater than (\>)1,500 per microliter (/µL), hemoglobin \>12 grams per deciliter (g/dL), platelets \>100,000/µL. CRu: disappearance of all symptoms and nearly all measurable lesions, but persistence of some radiologic abnormalities with normalization of all biologic abnormalities; normalization of the performance status for at least 3 months after the definite evaluation of therapy. PR: at least 50 percent (%) reduction of measurable and evaluable lymphoma involvement for at least 4 weeks without occurrence of new manifestations, normalization of blood counts. Participants without evaluation at end of induction/maintenance phase were considered nonresponders. |
| Failure-Free Survival (FFS), Percentage of Participants Estimated to be Free of Documented Disease Progression, Relapse, or Death | Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40 | FFS data were analyzed using Kaplan-Meier survival analysis. FFS was measured from the date of treatment start to the date of documented disease progression, relapse, or death from any cause. Responding participants, participants who were lost to follow up, who withdrew consent, or dropped out due to adverse events (AE) were censored at their last assessment date. The reported data refer to values up to 40 months. |
| FFS - Percentage of Participants With an Event | Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40 | FFS was measured from the date of treatment start to the date of documented disease progression, relapse, or death from any cause. Responding participants, participants who were lost to follow up, who withdrew consent, or who dropped out due to AEs were censored at their last assessment date. |
| FFS - Time to Event | Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40 | FFS was measured from the date of treatment start to the date of documented disease progression, relapse or death from any cause. Responding participants, participants who were lost to follow up, who withdrew consent or dropped out due to AEs were censored at their last assessment date. NOTE: The mean survival time and its standard error were underestimated because the largest observation was censored and the estimation was restricted to the largest event time. |
| Overall Survival (OS) - Percentage of Participants Estimated to be Alive | Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40 | OS data were analyzed using Kaplan-Meier survival analysis. OS was defined as the time from first dosage of study drug to the date of death from any cause. Reported data refer to values up to 40 months. |
| OS - Percentage of Participants With an Event | Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40. | OS was defined as the time from first dosage of study drug to the date of death from any cause. |
| Disease-Free Survival (DFS) - Percentage of Participants Estimated to be Disease-Free | Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40 | DFS data were analyzed using Kaplan-Meier survival analysis. DFS was defined for all participants who achieved a complete response (CR/CRu) at month 1 after the completion of treatment of the induction phase (Month 7 of the study) and was measured from the time of CR to the date of relapse. Participants without relapse were censored at their last assessment date. Participants who died due to tumour burden were considered in relapse. Participants who died due to any other causes were censored as of the death date. The reported data refer to values up to 40 months. |
| OS - Time to Event | Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40. | Overall survival was defined as the time from first dosage of study drug to the date of death from any cause. |
| DFS - Time to Event | Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40. | DFS was defined for all participants who achieved a complete response (CR/CRu) at month 1 after the completion of treatment of the induction phase (month 7 of the study) and was measured from the time of complete response to the date of relapse. Participants without relapse were censored at their last assessment date. Participants who died due to tumour burden were considered in relapse. Participants who died due to any other causes were censored on the death date. NOTE: The mean survival time and its standard error were underestimated because the largest observation was censored and the estimation was restricted to the largest event time. |
| Progression-free Survival (PFS) - Percentage of Participants Estimated to Be Progress Free | Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40 | PFS data were analyzed using Kaplan-Meier survival analysis. PFS was defined as the time from treatment start to the date of documented disease progression. Reported data refer to values up to 40 months. |
| PFS - Percentage of Participants With an Event | Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40 | Progression-free survival was defined as the time from the date of treatment start to the date of documented disease progression. |
| PFS - Time to Event | Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40 | Progression-free survival was defined as the time from treatment start to the date of documented disease progression. NOTE: The mean survival time and its standard error were underestimated because the largest observation was censored and the estimation was restricted to the largest event time. |
| Duration of Response (DR) - Percentage of Participants Expected to Maintain a Response | Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40 | DR data were analyzed using Kaplan-Meier survival analysis. DR was defined for all participants who achieved a response (CR, CRu and PR) at month 1 after the completion of treatment of the induction phase (Month 7 of the study) and was measured from the time of response until the date of progression or relapse. Participants without relapse or progression were censored at their last assessment date. Participants who died due to tumour were considered in progression. Participants who died for any other cause were censored to the death date. |
| DR - Percentage of Participants With an Event | Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40 | DR was defined for all participants who achieved a response (CR, CRu and PR) at month 1 after the completion of treatment of the induction phase (Month 7 of the study) and was measured from the time of response until the date of progression or relapse. Participants without relapse or progression were censored at their last assessment date. Participants who died due to tumour were considered in progression. Participants who died for any other cause were censored to the death date. |
| DR - Time to Event | Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40 | DR was defined for all participants who achieved a response (CR, CRu and PR) at month 1 after the completion of treatment of the induction phase (Month 7 of the study) and was measured from the time of response until the date of progression or relapse. Participants without relapse or progression were censored at their last assessment date. Participants who died due to tumour were considered in progression. Participants who died for any other cause were censored to the death date. |
| DFS - Percentage of Participants With an Event | Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40. | DFS was defined for all patients who achieved a complete response (CR/CRu) at month 1 after the completion of treatment of the induction phase (month 7 of the study) and was measured from the time of complete response to the date of relapse. Participants without relapse were censored at their last assessment date. Participants who died due to tumour burden were considered in relapse. Participants who died due to any other causes were censored on the death date. |
Countries
Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rituximab + Fludarabine + Cyclophosphamide Cycle 1 (28-day cycle): Participants received fludarabine 25 mg/m\^2 IV and cyclophosphamide 250 mg/m\^2 IV on Days 1, 2, and 3 and rituximab 375 mg/m\^2 IV on Day 8, followed by 20 days of rest. Cycles 2-3 and Cycle 6 (28-day cycle): Participants received rituximab 375 mg/m\^2 IV on Day 1 and fludarabine 25 mg/m\^2 IV and cyclophosphamide 250 mg/m\^2 IV on Days 2, 3, and 4 followed by 24 days of rest. Cycles 4-5 (28-day cycle): Participants received fludarabine 25 mg/m\^2 IV and cyclophosphamide 250 mg/m\^2 IV on Days 2, 3, and 4 and rituximab 375 mg/m\^2 IV on Day 14, followed by 14 days of rest. Cycles 7-10 (2-month cycle): Following 2 months rest after the completion of Cycle 6, participants with CR, CRu, or PR, received maintenance therapy with rituximab 375 mg/m\^2 IV on Day 1, followed by 2 months rest; cycle was repeated 4 times. | 46 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Follow-up (Months 17-40 of Study) | Adverse Event | 1 |
| Follow-up (Months 17-40 of Study) | Disease progression | 2 |
| Follow-up (Months 17-40 of Study) | Protocol Violation | 1 |
| Induction Phase (Months 1 to 7 of Study) | Adverse Event | 2 |
| Induction Phase (Months 1 to 7 of Study) | Withdrawal by Subject | 1 |
| Maintenance Phase (Months 8-16 of Study) | Adverse Event | 2 |
| Maintenance Phase (Months 8-16 of Study) | Clinical relapse | 1 |
Baseline characteristics
| Characteristic | Rituximab + Fludarabine + Cyclophosphamide |
|---|---|
| Age, Continuous | 57.3 years STANDARD_DEVIATION 8.2 |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 47 / 47 |
| serious Total, serious adverse events | 16 / 47 |
Outcome results
Primary
Percentage of Participants Remaining Failure-Free After 2 Years From Treatment Start Date
Percentage of participants who at 2 years from the start of treatment remained free from documented disease progression, relapse, or death. Failure status was based on tumor evaluation performed on Month 28. Participants who did not have a tumor evaluation at Month 28 were counted as failures.
Time frame: Month 28
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab + Fludarabine + Cyclophosphamide | Percentage of Participants Remaining Failure-Free After 2 Years From Treatment Start Date | 73.9 percentage of participants |
p-value: <0.0001t-test, 2 sided
Secondary
DFS - Percentage of Participants With an Event
DFS was defined for all patients who achieved a complete response (CR/CRu) at month 1 after the completion of treatment of the induction phase (month 7 of the study) and was measured from the time of complete response to the date of relapse. Participants without relapse were censored at their last assessment date. Participants who died due to tumour burden were considered in relapse. Participants who died due to any other causes were censored on the death date.
Time frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40.
Population: ITT population; only participants who achieved a complete response (CR/CRu) at month 1 after the completion of treatment of the induction phase were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab + Fludarabine + Cyclophosphamide | DFS - Percentage of Participants With an Event | 10.34 percentage of participants |
Secondary
DFS - Time to Event
DFS was defined for all participants who achieved a complete response (CR/CRu) at month 1 after the completion of treatment of the induction phase (month 7 of the study) and was measured from the time of complete response to the date of relapse. Participants without relapse were censored at their last assessment date. Participants who died due to tumour burden were considered in relapse. Participants who died due to any other causes were censored on the death date. NOTE: The mean survival time and its standard error were underestimated because the largest observation was censored and the estimation was restricted to the largest event time.
Time frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40.
Population: ITT population; only participants who achieved a complete response (CR/CRu) at month 1 after the completion of treatment of the induction phase were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rituximab + Fludarabine + Cyclophosphamide | DFS - Time to Event | 32.51 months | Standard Error 0.58 |
Secondary
Disease-Free Survival (DFS) - Percentage of Participants Estimated to be Disease-Free
DFS data were analyzed using Kaplan-Meier survival analysis. DFS was defined for all participants who achieved a complete response (CR/CRu) at month 1 after the completion of treatment of the induction phase (Month 7 of the study) and was measured from the time of CR to the date of relapse. Participants without relapse were censored at their last assessment date. Participants who died due to tumour burden were considered in relapse. Participants who died due to any other causes were censored as of the death date. The reported data refer to values up to 40 months.
Time frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40
Population: ITT population; only participants who achieved a complete response (CR/CRu) at month 1 after the completion of treatment of the induction phase were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab + Fludarabine + Cyclophosphamide | Disease-Free Survival (DFS) - Percentage of Participants Estimated to be Disease-Free | 87.70 percentage of participants |
Secondary
DR - Percentage of Participants With an Event
DR was defined for all participants who achieved a response (CR, CRu and PR) at month 1 after the completion of treatment of the induction phase (Month 7 of the study) and was measured from the time of response until the date of progression or relapse. Participants without relapse or progression were censored at their last assessment date. Participants who died due to tumour were considered in progression. Participants who died for any other cause were censored to the death date.
Time frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40
Population: ITT population; only participants who achieved a response (CR, CRu and PR) at month 1 after the completion of treatment of the induction phase of the study were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab + Fludarabine + Cyclophosphamide | DR - Percentage of Participants With an Event | 9.09 percentage of participants |
Secondary
DR - Time to Event
DR was defined for all participants who achieved a response (CR, CRu and PR) at month 1 after the completion of treatment of the induction phase (Month 7 of the study) and was measured from the time of response until the date of progression or relapse. Participants without relapse or progression were censored at their last assessment date. Participants who died due to tumour were considered in progression. Participants who died for any other cause were censored to the death date.
Time frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40
Population: ITT population: only participants who achieved a response (CR, CRu and PR) at month 1 after the completion of treatment of the induction phase of the study were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rituximab + Fludarabine + Cyclophosphamide | DR - Time to Event | 32.19 months | Standard Error 0.72 |
Secondary
Duration of Response (DR) - Percentage of Participants Expected to Maintain a Response
DR data were analyzed using Kaplan-Meier survival analysis. DR was defined for all participants who achieved a response (CR, CRu and PR) at month 1 after the completion of treatment of the induction phase (Month 7 of the study) and was measured from the time of response until the date of progression or relapse. Participants without relapse or progression were censored at their last assessment date. Participants who died due to tumour were considered in progression. Participants who died for any other cause were censored to the death date.
Time frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40
Population: ITT population; only participants who achieved a response (CR, CRu and PR) at month 1 after the completion of treatment of the induction phase of the study were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab + Fludarabine + Cyclophosphamide | Duration of Response (DR) - Percentage of Participants Expected to Maintain a Response | 90.07 percentage of participants |
Secondary
Failure-Free Survival (FFS), Percentage of Participants Estimated to be Free of Documented Disease Progression, Relapse, or Death
FFS data were analyzed using Kaplan-Meier survival analysis. FFS was measured from the date of treatment start to the date of documented disease progression, relapse, or death from any cause. Responding participants, participants who were lost to follow up, who withdrew consent, or dropped out due to adverse events (AE) were censored at their last assessment date. The reported data refer to values up to 40 months.
Time frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab + Fludarabine + Cyclophosphamide | Failure-Free Survival (FFS), Percentage of Participants Estimated to be Free of Documented Disease Progression, Relapse, or Death | 90.12 percentage of participants |
Secondary
FFS - Percentage of Participants With an Event
FFS was measured from the date of treatment start to the date of documented disease progression, relapse, or death from any cause. Responding participants, participants who were lost to follow up, who withdrew consent, or who dropped out due to AEs were censored at their last assessment date.
Time frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab + Fludarabine + Cyclophosphamide | FFS - Percentage of Participants With an Event | 8.7 percentage of participants |
Secondary
FFS - Time to Event
FFS was measured from the date of treatment start to the date of documented disease progression, relapse or death from any cause. Responding participants, participants who were lost to follow up, who withdrew consent or dropped out due to AEs were censored at their last assessment date. NOTE: The mean survival time and its standard error were underestimated because the largest observation was censored and the estimation was restricted to the largest event time.
Time frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rituximab + Fludarabine + Cyclophosphamide | FFS - Time to Event | 39.14 months | Standard Error 0.7 |
Secondary
OS - Percentage of Participants With an Event
OS was defined as the time from first dosage of study drug to the date of death from any cause.
Time frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40.
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab + Fludarabine + Cyclophosphamide | OS - Percentage of Participants With an Event | 2.17 percentage of participants |
Secondary
OS - Time to Event
Overall survival was defined as the time from first dosage of study drug to the date of death from any cause.
Time frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40.
Population: ITT population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Rituximab + Fludarabine + Cyclophosphamide | OS - Time to Event | 38.6 months |
Secondary
Overall Survival (OS) - Percentage of Participants Estimated to be Alive
OS data were analyzed using Kaplan-Meier survival analysis. OS was defined as the time from first dosage of study drug to the date of death from any cause. Reported data refer to values up to 40 months.
Time frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab + Fludarabine + Cyclophosphamide | Overall Survival (OS) - Percentage of Participants Estimated to be Alive | 97.44 percentage of participants |
Secondary
Percentage of Participants Achieving a Best Overall Response of CR, CRu, or PR by Study Phase
CR: complete disappearance of all symptoms/objective signs of disease (enlarged lymph nodes, hepatomegaly, splenomegaly) for at least 3 months following definitive re-evaluation at end of therapy. For initial bone marrow involvement, clearance of bone marrow documented by biopsy, normalization of blood counts with granulocytes greater than (\>)1,500 per microliter (/µL), hemoglobin \>12 grams per deciliter (g/dL), platelets \>100,000/µL. CRu: disappearance of all symptoms and nearly all measurable lesions, but persistence of some radiologic abnormalities with normalization of all biologic abnormalities; normalization of the performance status for at least 3 months after the definite evaluation of therapy. PR: at least 50 percent (%) reduction of measurable and evaluable lymphoma involvement for at least 4 weeks without occurrence of new manifestations, normalization of blood counts. Participants without evaluation at end of induction/maintenance phase were considered nonresponders.
Time frame: Baseline, Months 4, 7 (Induction Phase), 11, 16 (Maintenance Phase),22, 28, 34, and 40(Follow-Up Phase)
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab + Fludarabine + Cyclophosphamide | Percentage of Participants Achieving a Best Overall Response of CR, CRu, or PR by Study Phase | Induction Phase | 95.7 percentage of participants |
| Rituximab + Fludarabine + Cyclophosphamide | Percentage of Participants Achieving a Best Overall Response of CR, CRu, or PR by Study Phase | Maintenance Phase | 80.4 percentage of participants |
Secondary
Percentage of Participants Achieving a Response by Response Type and Study Phase
CR: complete disappearance of all symptoms/objective signs of disease (enlarged lymph nodes, hepatomegaly, splenomegaly) for at least 3 months following definitive re-evaluation at end of therapy. For initial bone marrow involvement, clearance of bone marrow documented by biopsy, normalization of blood counts with granulocytes greater than (\>)1,500 per microliter (/µL), hemoglobin \>12 grams per deciliter (g/dL), platelets \>100,000/µL. CRu: disappearance of all symptoms and nearly all measurable lesions, but persistence of some radiologic abnormalities with normalization of all biologic abnormalities; normalization of the performance status for at least 3 months after the definite evaluation of therapy. PR: at least 50 percent (%) reduction of measurable and evaluable lymphoma involvement for at least 4 weeks without occurrence of new manifestations, normalization of blood counts. Participants without evaluation at end of induction/maintenance phase were considered nonresponders.
Time frame: Baseline, Months 4, 7, 11, 16, 22, 28, 34, and 40
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab + Fludarabine + Cyclophosphamide | Percentage of Participants Achieving a Response by Response Type and Study Phase | CR at end of induction phase | 41.3 percentage of participants |
| Rituximab + Fludarabine + Cyclophosphamide | Percentage of Participants Achieving a Response by Response Type and Study Phase | CR at end of maintenance phase | 45.7 percentage of participants |
| Rituximab + Fludarabine + Cyclophosphamide | Percentage of Participants Achieving a Response by Response Type and Study Phase | CR at final assessment | 45.7 percentage of participants |
| Rituximab + Fludarabine + Cyclophosphamide | Percentage of Participants Achieving a Response by Response Type and Study Phase | CRu at end of induction phase | 21.7 percentage of participants |
| Rituximab + Fludarabine + Cyclophosphamide | Percentage of Participants Achieving a Response by Response Type and Study Phase | CRu at end of maintenance phase | 15.2 percentage of participants |
| Rituximab + Fludarabine + Cyclophosphamide | Percentage of Participants Achieving a Response by Response Type and Study Phase | CRu at final assessment | 19.6 percentage of participants |
| Rituximab + Fludarabine + Cyclophosphamide | Percentage of Participants Achieving a Response by Response Type and Study Phase | PR at end of induction phase | 32.6 percentage of participants |
| Rituximab + Fludarabine + Cyclophosphamide | Percentage of Participants Achieving a Response by Response Type and Study Phase | PR at end of maintenance phase | 19.6 percentage of participants |
| Rituximab + Fludarabine + Cyclophosphamide | Percentage of Participants Achieving a Response by Response Type and Study Phase | PR at final assessment | 13.0 percentage of participants |
| Rituximab + Fludarabine + Cyclophosphamide | Percentage of Participants Achieving a Response by Response Type and Study Phase | Relapse at end of induction phase | 0 percentage of participants |
| Rituximab + Fludarabine + Cyclophosphamide | Percentage of Participants Achieving a Response by Response Type and Study Phase | Relapse at end of maintenance phase | 0 percentage of participants |
| Rituximab + Fludarabine + Cyclophosphamide | Percentage of Participants Achieving a Response by Response Type and Study Phase | Relapse at final assessment | 2.2 percentage of participants |
| Rituximab + Fludarabine + Cyclophosphamide | Percentage of Participants Achieving a Response by Response Type and Study Phase | Unknown at end of induction phase | 4.3 percentage of participants |
| Rituximab + Fludarabine + Cyclophosphamide | Percentage of Participants Achieving a Response by Response Type and Study Phase | Unknown at end of maintenance phase | 19.6 percentage of participants |
| Rituximab + Fludarabine + Cyclophosphamide | Percentage of Participants Achieving a Response by Response Type and Study Phase | Unknown at final assessment | 19.6 percentage of participants |
Secondary
PFS - Percentage of Participants With an Event
Progression-free survival was defined as the time from the date of treatment start to the date of documented disease progression.
Time frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab + Fludarabine + Cyclophosphamide | PFS - Percentage of Participants With an Event | 8.70 percentage of participants |
Secondary
PFS - Time to Event
Progression-free survival was defined as the time from treatment start to the date of documented disease progression. NOTE: The mean survival time and its standard error were underestimated because the largest observation was censored and the estimation was restricted to the largest event time.
Time frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rituximab + Fludarabine + Cyclophosphamide | PFS - Time to Event | 39.14 months | Standard Error 0.7 |
Secondary
Progression-free Survival (PFS) - Percentage of Participants Estimated to Be Progress Free
PFS data were analyzed using Kaplan-Meier survival analysis. PFS was defined as the time from treatment start to the date of documented disease progression. Reported data refer to values up to 40 months.
Time frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab + Fludarabine + Cyclophosphamide | Progression-free Survival (PFS) - Percentage of Participants Estimated to Be Progress Free | 90.12 percentage of participants |