Trial Outcomes & Findings for A Study of MabThera (Rituximab) in Patients With Advanced Non-Hodgkin's Lymphoma (NCT NCT00269113)
NCT ID: NCT00269113
Last Updated: 2015-07-23
Results Overview
CR was defined as a complete remission of all objective medical findings at the time of restaging, with complete resolution of pre-existing swelling of the lymph nodes, as well as a pre-existing hepatomegaly and splenomegaly, for at least 4 weeks. This was in exclusion of persistent lymphoma infiltration of the bone marrow by means of bone marrow biopsy; normalization of blood counts with granulocytes greater than (\>)1.5 giga particles per liter (Gpt/L) (which is the equivalent of 10\^9/L), hemoglobin (Hb) \>7.5 millimoles per liter (mmol/L), and platelets less than (\<) 100 Gpt/L. PR was defined as greater than or equal to (≥)50 percent (%) reduction of all measurable and evaluable lymphoma manifestations (sum of the products of the 2 largest perpendicular diameters) for at least 4 weeks without occurrence of new manifestations and normalization of blood counts.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
360 participants
Primary outcome timeframe
Following completion of 6 cycles (24 weeks)
Results posted on
2015-07-23
Participant Flow
Participant milestones
| Measure |
Mitoxantrone, Chlorambucil, Prednisolone (MCP)
Participants received mitoxantrone 8 milligrams per square meter (mg/m\^2), intravenously (IV), on Days 1 and 2, chlorambucil 3 times (x) 3 mg/m\^2, by mouth (PO), every 8 hours on Days 1 through 5, and prednisolone at 25 mg/m\^2, PO on Days 1 through 5. This cycle was repeated at 4-week intervals for a minimum of 6 cycles and a maximum of 8 cycles. After Cycles 2 and 6, participants were assessed for response; participants with no change or with progressive disease (or with minimal response at Cycle 6) were withdrawn from therapy. Participants achieving a complete remission (CR) or partial remission (PR) following induction therapy with MCP were administered maintenance therapy (per standard of care and at the discretion of the investigator) with interferon (IFN) alpha 3 x 4.5 million international units (IU) per week, subcutaneously (SC), until progression or withdrawal. Participants could have also received 3 x 500 mg of paracetamol/day during the first weeks of IFN therapy.
|
Rituximab + MCP
Participants received rituximab 375 mg/m\^2, IV on Day 1, mitoxantrone 8 mg/m\^2, IV, on Days 3 and 4, chlorambucil 3 x 3 mg/m\^2, PO every 8 hours on Days 3 through 7, and prednisolone 25 mg/m\^2, PO on Days 3 through 7. This cycle was repeated at 4-week intervals for a minimum of 6 cycles and a maximum of 8 cycles. After Cycles 2 and 6, participants were assessed for response; participants with no change or with progressive disease (or with minimal response at Cycle 6) were withdrawn from therapy. Participants achieving a CR or PR following induction therapy with MCP were administered maintenance therapy (per standard of care and at the discretion of the investigator) with IFN alpha 3 x 4.5 mIU per week, SC, until progression or withdrawal. Participants could have also received 3 x 500 mg of paracetamol/day during the first weeks of IFN therapy.
|
|---|---|---|
|
Overall Study
STARTED
|
177
|
183
|
|
Overall Study
COMPLETED
|
103
|
146
|
|
Overall Study
NOT COMPLETED
|
74
|
37
|
Reasons for withdrawal
| Measure |
Mitoxantrone, Chlorambucil, Prednisolone (MCP)
Participants received mitoxantrone 8 milligrams per square meter (mg/m\^2), intravenously (IV), on Days 1 and 2, chlorambucil 3 times (x) 3 mg/m\^2, by mouth (PO), every 8 hours on Days 1 through 5, and prednisolone at 25 mg/m\^2, PO on Days 1 through 5. This cycle was repeated at 4-week intervals for a minimum of 6 cycles and a maximum of 8 cycles. After Cycles 2 and 6, participants were assessed for response; participants with no change or with progressive disease (or with minimal response at Cycle 6) were withdrawn from therapy. Participants achieving a complete remission (CR) or partial remission (PR) following induction therapy with MCP were administered maintenance therapy (per standard of care and at the discretion of the investigator) with interferon (IFN) alpha 3 x 4.5 million international units (IU) per week, subcutaneously (SC), until progression or withdrawal. Participants could have also received 3 x 500 mg of paracetamol/day during the first weeks of IFN therapy.
|
Rituximab + MCP
Participants received rituximab 375 mg/m\^2, IV on Day 1, mitoxantrone 8 mg/m\^2, IV, on Days 3 and 4, chlorambucil 3 x 3 mg/m\^2, PO every 8 hours on Days 3 through 7, and prednisolone 25 mg/m\^2, PO on Days 3 through 7. This cycle was repeated at 4-week intervals for a minimum of 6 cycles and a maximum of 8 cycles. After Cycles 2 and 6, participants were assessed for response; participants with no change or with progressive disease (or with minimal response at Cycle 6) were withdrawn from therapy. Participants achieving a CR or PR following induction therapy with MCP were administered maintenance therapy (per standard of care and at the discretion of the investigator) with IFN alpha 3 x 4.5 mIU per week, SC, until progression or withdrawal. Participants could have also received 3 x 500 mg of paracetamol/day during the first weeks of IFN therapy.
|
|---|---|---|
|
Overall Study
Adverse Event
|
14
|
7
|
|
Overall Study
Lack of Efficacy
|
35
|
18
|
|
Overall Study
Early Improvement
|
2
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
2
|
|
Overall Study
Death
|
6
|
2
|
|
Overall Study
Lost to Follow-up
|
2
|
1
|
|
Overall Study
Protocol Violation
|
15
|
5
|
|
Overall Study
Other
|
0
|
2
|
Baseline Characteristics
A Study of MabThera (Rituximab) in Patients With Advanced Non-Hodgkin's Lymphoma
Baseline characteristics by cohort
| Measure |
Mitoxantrone, Chlorambucil, Prednisolone (MCP)
n=177 Participants
Participants received mitoxantrone 8 mg/m\^2, IV, on Days 1 and 2, chlorambucil 3 x 3 mg/m\^2, PO, every 8 hours on Days 1 through 5, and prednisolone at 25 mg/m\^2, PO on Days 1 through 5. This cycle was repeated at 4-week intervals for a minimum of 6 cycles and a maximum of 8 cycles. After Cycles 2 and 6, participants were assessed for response; participants with no change or with progressive disease (or with minimal response at Cycle 6) were withdrawn from therapy. Participants achieving a CR or PR following induction therapy with MCP were administered maintenance therapy (per standard of care and at the discretion of the investigator) with IFN alpha 3 x 4.5 mIU per week, SC, until progression or withdrawal. Participants could have also received 3 x 500 mg of paracetamol/day during the first weeks of IFN therapy.
|
Rituximab + MCP
n=181 Participants
Participants received rituximab 375 mg/m\^2, IV on Day 1, mitoxantrone 8 mg/m\^2, IV, on Days 3 and 4, chlorambucil 3 x 3 mg/m\^2, PO every 8 hours on Days 3 through 7, and prednisolone 25 mg/m\^2, PO on Days 3 through 7. This cycle was repeated at 4-week intervals for a minimum of 6 cycles and a maximum of 8 cycles. After Cycles 2 and 6, participants were assessed for response; participants with no change or with progressive disease (or with minimal response at Cycle 6) were withdrawn from therapy. Participants achieving a CR or PR following induction therapy with MCP were administered maintenance therapy (per standard of care and at the discretion of the investigator) with IFN alpha 3 x 4.5 mIU per week, SC, until progression or withdrawal. Participants could have also received 3 x 500 mg of paracetamol/day during the first weeks of IFN therapy.
|
Total
n=358 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
60.1 years
STANDARD_DEVIATION 8.7 • n=99 Participants
|
60.4 years
STANDARD_DEVIATION 8.3 • n=107 Participants
|
60.4 years
STANDARD_DEVIATION 8.5 • n=206 Participants
|
|
Sex: Female, Male
Female
|
89 Participants
n=99 Participants
|
79 Participants
n=107 Participants
|
168 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
88 Participants
n=99 Participants
|
102 Participants
n=107 Participants
|
190 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Following completion of 6 cycles (24 weeks)Population: The ITT centroblastic-centrocytic (cbcc)/Follicular Lymphoma (FL) (collectively, ITTcbcc/FL) population included all participants in the ITT population with cbcc lymphoma (target population).
CR was defined as a complete remission of all objective medical findings at the time of restaging, with complete resolution of pre-existing swelling of the lymph nodes, as well as a pre-existing hepatomegaly and splenomegaly, for at least 4 weeks. This was in exclusion of persistent lymphoma infiltration of the bone marrow by means of bone marrow biopsy; normalization of blood counts with granulocytes greater than (\>)1.5 giga particles per liter (Gpt/L) (which is the equivalent of 10\^9/L), hemoglobin (Hb) \>7.5 millimoles per liter (mmol/L), and platelets less than (\<) 100 Gpt/L. PR was defined as greater than or equal to (≥)50 percent (%) reduction of all measurable and evaluable lymphoma manifestations (sum of the products of the 2 largest perpendicular diameters) for at least 4 weeks without occurrence of new manifestations and normalization of blood counts.
Outcome measures
| Measure |
Mitoxantrone, Chlorambucil, Prednisolone (MCP)
n=96 Participants
Participants received mitoxantrone 8 mg/m\^2, IV, on Days 1 and 2, chlorambucil 3 x 3 mg/m\^2, PO, every 8 hours on Days 1 through 5, and prednisolone at 25 mg/m\^2, PO on Days 1 through 5. This cycle was repeated at 4-week intervals for a minimum of 6 cycles and a maximum of 8 cycles. After Cycles 2 and 6, participants were assessed for response; participants with no change or with progressive disease (or with minimal response at Cycle 6) were withdrawn from therapy. Participants achieving a CR or PR following induction therapy with MCP were administered maintenance therapy (per standard of care and at the discretion of the investigator) with IFN alpha 3 x 4.5 mIU per week, SC, until progression or withdrawal. Participants could have also received 3 x 500 mg of paracetamol/day during the first weeks of IFN therapy.
|
Rituximab + MCP
n=105 Participants
Participants received rituximab 375 mg/m\^2, IV on Day 1, mitoxantrone 8 mg/m\^2, IV, on Days 3 and 4, chlorambucil 3 x 3 mg/m\^2, PO every 8 hours on Days 3 through 7, and prednisolone 25 mg/m\^2, PO on Days 3 through 7. This cycle was repeated at 4-week intervals for a minimum of 6 cycles and a maximum of 8 cycles. After Cycles 2 and 6, participants were assessed for response; participants with no change or with progressive disease (or with minimal response at Cycle 6) were withdrawn from therapy. Participants achieving a CR or PR following induction therapy with MCP were administered maintenance therapy (per standard of care and at the discretion of the investigator) with IFN alpha 3 x 4.5 mIU per week, SC, until progression or withdrawal. Participants could have also received 3 x 500 mg of paracetamol/day during the first weeks of IFN therapy.
|
|---|---|---|
|
Percentage of Participants Achieving CR or PR at the End of Therapy
|
75.0 percentage of participants
Interval 65.1 to 83.3
|
92.4 percentage of participants
Interval 85.5 to 96.7
|
SECONDARY outcome
Timeframe: 24 monthsPopulation: ITTcbcc/FL Population
PFS was defined as the interval from randomization date to progression of disease or death from non-Hodgkin's Lymphoma (NHL). Progression of disease was defined as: increase in the frequency and severity of disease symptoms; occurrence of new nodal or extranodal lymphoma manifestations; volume increase of pre-existing lymphoma manifestations by more than 25%; or increase of splenomegaly by more than 25%. Data were analyzed by means of Kaplan-Meier estimators and log-rank tests at the significance level of alpha equals (=) 5% for difference between the treatment groups.
Outcome measures
| Measure |
Mitoxantrone, Chlorambucil, Prednisolone (MCP)
n=96 Participants
Participants received mitoxantrone 8 mg/m\^2, IV, on Days 1 and 2, chlorambucil 3 x 3 mg/m\^2, PO, every 8 hours on Days 1 through 5, and prednisolone at 25 mg/m\^2, PO on Days 1 through 5. This cycle was repeated at 4-week intervals for a minimum of 6 cycles and a maximum of 8 cycles. After Cycles 2 and 6, participants were assessed for response; participants with no change or with progressive disease (or with minimal response at Cycle 6) were withdrawn from therapy. Participants achieving a CR or PR following induction therapy with MCP were administered maintenance therapy (per standard of care and at the discretion of the investigator) with IFN alpha 3 x 4.5 mIU per week, SC, until progression or withdrawal. Participants could have also received 3 x 500 mg of paracetamol/day during the first weeks of IFN therapy.
|
Rituximab + MCP
n=105 Participants
Participants received rituximab 375 mg/m\^2, IV on Day 1, mitoxantrone 8 mg/m\^2, IV, on Days 3 and 4, chlorambucil 3 x 3 mg/m\^2, PO every 8 hours on Days 3 through 7, and prednisolone 25 mg/m\^2, PO on Days 3 through 7. This cycle was repeated at 4-week intervals for a minimum of 6 cycles and a maximum of 8 cycles. After Cycles 2 and 6, participants were assessed for response; participants with no change or with progressive disease (or with minimal response at Cycle 6) were withdrawn from therapy. Participants achieving a CR or PR following induction therapy with MCP were administered maintenance therapy (per standard of care and at the discretion of the investigator) with IFN alpha 3 x 4.5 mIU per week, SC, until progression or withdrawal. Participants could have also received 3 x 500 mg of paracetamol/day during the first weeks of IFN therapy.
|
|---|---|---|
|
Progression-Free Survival (PFS) - Percentage of Participants Event Free at 24 Months
|
57.6 percentage of participants
|
86.7 percentage of participants
|
SECONDARY outcome
Timeframe: Month 24Population: ITTcbcc/FL Population
OS was defined as interval from randomization to date of death of any cause. Data were analyzed by means of Kaplan-Meier estimators and log-rank tests at the significance level of alpha=5% for difference between the treatment groups.
Outcome measures
| Measure |
Mitoxantrone, Chlorambucil, Prednisolone (MCP)
n=96 Participants
Participants received mitoxantrone 8 mg/m\^2, IV, on Days 1 and 2, chlorambucil 3 x 3 mg/m\^2, PO, every 8 hours on Days 1 through 5, and prednisolone at 25 mg/m\^2, PO on Days 1 through 5. This cycle was repeated at 4-week intervals for a minimum of 6 cycles and a maximum of 8 cycles. After Cycles 2 and 6, participants were assessed for response; participants with no change or with progressive disease (or with minimal response at Cycle 6) were withdrawn from therapy. Participants achieving a CR or PR following induction therapy with MCP were administered maintenance therapy (per standard of care and at the discretion of the investigator) with IFN alpha 3 x 4.5 mIU per week, SC, until progression or withdrawal. Participants could have also received 3 x 500 mg of paracetamol/day during the first weeks of IFN therapy.
|
Rituximab + MCP
n=105 Participants
Participants received rituximab 375 mg/m\^2, IV on Day 1, mitoxantrone 8 mg/m\^2, IV, on Days 3 and 4, chlorambucil 3 x 3 mg/m\^2, PO every 8 hours on Days 3 through 7, and prednisolone 25 mg/m\^2, PO on Days 3 through 7. This cycle was repeated at 4-week intervals for a minimum of 6 cycles and a maximum of 8 cycles. After Cycles 2 and 6, participants were assessed for response; participants with no change or with progressive disease (or with minimal response at Cycle 6) were withdrawn from therapy. Participants achieving a CR or PR following induction therapy with MCP were administered maintenance therapy (per standard of care and at the discretion of the investigator) with IFN alpha 3 x 4.5 mIU per week, SC, until progression or withdrawal. Participants could have also received 3 x 500 mg of paracetamol/day during the first weeks of IFN therapy.
|
|---|---|---|
|
Overall Survival (OS) - Percentage of Participants Alive at 24 Months
|
78.8 percentage of participants
|
93.7 percentage of participants
|
SECONDARY outcome
Timeframe: Month 24Population: ITTcbcc/FL Population
EFS was defined as the interval from randomization date to therapy failure. Therapy failure was defined after 2 cycles as no change (NC) or progression of disease (PD); after 6 cycles as minimal response \[MR\], NC, or PD); or death from any cause. NC is defined as tumor regression of \<25%, stable disease and progression ≤25%. PD was defined as the increase in the frequency and severity of disease symptoms, occurrence of new nodal or extranodal lymphoma manifestations, volume increase of pre-existing lymphoma manifestations by more than 25%, and increase of splenomegaly by more than 25%. MR was defined as tumor regression between 50% (\<50%) and 25% (≥25%) for at least 4 weeks without occurrence of new manifestations. Data were analyzed by means of Kaplan-Meier estimators and log-rank tests at the significance level of alpha=5% for difference between the treatment groups.
Outcome measures
| Measure |
Mitoxantrone, Chlorambucil, Prednisolone (MCP)
n=96 Participants
Participants received mitoxantrone 8 mg/m\^2, IV, on Days 1 and 2, chlorambucil 3 x 3 mg/m\^2, PO, every 8 hours on Days 1 through 5, and prednisolone at 25 mg/m\^2, PO on Days 1 through 5. This cycle was repeated at 4-week intervals for a minimum of 6 cycles and a maximum of 8 cycles. After Cycles 2 and 6, participants were assessed for response; participants with no change or with progressive disease (or with minimal response at Cycle 6) were withdrawn from therapy. Participants achieving a CR or PR following induction therapy with MCP were administered maintenance therapy (per standard of care and at the discretion of the investigator) with IFN alpha 3 x 4.5 mIU per week, SC, until progression or withdrawal. Participants could have also received 3 x 500 mg of paracetamol/day during the first weeks of IFN therapy.
|
Rituximab + MCP
n=105 Participants
Participants received rituximab 375 mg/m\^2, IV on Day 1, mitoxantrone 8 mg/m\^2, IV, on Days 3 and 4, chlorambucil 3 x 3 mg/m\^2, PO every 8 hours on Days 3 through 7, and prednisolone 25 mg/m\^2, PO on Days 3 through 7. This cycle was repeated at 4-week intervals for a minimum of 6 cycles and a maximum of 8 cycles. After Cycles 2 and 6, participants were assessed for response; participants with no change or with progressive disease (or with minimal response at Cycle 6) were withdrawn from therapy. Participants achieving a CR or PR following induction therapy with MCP were administered maintenance therapy (per standard of care and at the discretion of the investigator) with IFN alpha 3 x 4.5 mIU per week, SC, until progression or withdrawal. Participants could have also received 3 x 500 mg of paracetamol/day during the first weeks of IFN therapy.
|
|---|---|---|
|
Event-Free Survival (EFS) - Percentage of Participants Event Free at 24 Months
|
50.9 percentage of participants
|
83.6 percentage of participants
|
SECONDARY outcome
Timeframe: Month 24Population: ITTcbcc/FL Population
DFS was defined as the interval from first assessment of CR to PD. PD is an increase in the frequency and severity of disease symptoms, the occurrence of new nodal or extranodal lymphoma manifestations, the volume increase of pre-existing lymphoma manifestations by more than 25%, increase of splenomegaly by more than 25%. Data were analyzed by means of Kaplan-Meier estimators and log-rank tests at the significance level of alpha=5% for difference between the treatment groups.
Outcome measures
| Measure |
Mitoxantrone, Chlorambucil, Prednisolone (MCP)
n=96 Participants
Participants received mitoxantrone 8 mg/m\^2, IV, on Days 1 and 2, chlorambucil 3 x 3 mg/m\^2, PO, every 8 hours on Days 1 through 5, and prednisolone at 25 mg/m\^2, PO on Days 1 through 5. This cycle was repeated at 4-week intervals for a minimum of 6 cycles and a maximum of 8 cycles. After Cycles 2 and 6, participants were assessed for response; participants with no change or with progressive disease (or with minimal response at Cycle 6) were withdrawn from therapy. Participants achieving a CR or PR following induction therapy with MCP were administered maintenance therapy (per standard of care and at the discretion of the investigator) with IFN alpha 3 x 4.5 mIU per week, SC, until progression or withdrawal. Participants could have also received 3 x 500 mg of paracetamol/day during the first weeks of IFN therapy.
|
Rituximab + MCP
n=105 Participants
Participants received rituximab 375 mg/m\^2, IV on Day 1, mitoxantrone 8 mg/m\^2, IV, on Days 3 and 4, chlorambucil 3 x 3 mg/m\^2, PO every 8 hours on Days 3 through 7, and prednisolone 25 mg/m\^2, PO on Days 3 through 7. This cycle was repeated at 4-week intervals for a minimum of 6 cycles and a maximum of 8 cycles. After Cycles 2 and 6, participants were assessed for response; participants with no change or with progressive disease (or with minimal response at Cycle 6) were withdrawn from therapy. Participants achieving a CR or PR following induction therapy with MCP were administered maintenance therapy (per standard of care and at the discretion of the investigator) with IFN alpha 3 x 4.5 mIU per week, SC, until progression or withdrawal. Participants could have also received 3 x 500 mg of paracetamol/day during the first weeks of IFN therapy.
|
|---|---|---|
|
Disease-Free Survival (DFS) - Percentage of Participants Event Free at 24 Months
|
69.6 percentage of participants
|
86.5 percentage of participants
|
SECONDARY outcome
Timeframe: Month 24Population: ITTcbcc/FL Population
Response duration defined as interval from first assessment of CR/PR to PD. PD is an increase in the frequency and severity of disease symptoms, occurrence of new nodal or extranodal lymphoma manifestations, volume increase of pre-existing lymphoma manifestations by more than 25%, increase of splenomegaly by more than 25%. Data were analyzed by means of Kaplan-Meier estimators and log-rank tests at the significance level of alpha=5% for difference between the treatment groups.
Outcome measures
| Measure |
Mitoxantrone, Chlorambucil, Prednisolone (MCP)
n=96 Participants
Participants received mitoxantrone 8 mg/m\^2, IV, on Days 1 and 2, chlorambucil 3 x 3 mg/m\^2, PO, every 8 hours on Days 1 through 5, and prednisolone at 25 mg/m\^2, PO on Days 1 through 5. This cycle was repeated at 4-week intervals for a minimum of 6 cycles and a maximum of 8 cycles. After Cycles 2 and 6, participants were assessed for response; participants with no change or with progressive disease (or with minimal response at Cycle 6) were withdrawn from therapy. Participants achieving a CR or PR following induction therapy with MCP were administered maintenance therapy (per standard of care and at the discretion of the investigator) with IFN alpha 3 x 4.5 mIU per week, SC, until progression or withdrawal. Participants could have also received 3 x 500 mg of paracetamol/day during the first weeks of IFN therapy.
|
Rituximab + MCP
n=105 Participants
Participants received rituximab 375 mg/m\^2, IV on Day 1, mitoxantrone 8 mg/m\^2, IV, on Days 3 and 4, chlorambucil 3 x 3 mg/m\^2, PO every 8 hours on Days 3 through 7, and prednisolone 25 mg/m\^2, PO on Days 3 through 7. This cycle was repeated at 4-week intervals for a minimum of 6 cycles and a maximum of 8 cycles. After Cycles 2 and 6, participants were assessed for response; participants with no change or with progressive disease (or with minimal response at Cycle 6) were withdrawn from therapy. Participants achieving a CR or PR following induction therapy with MCP were administered maintenance therapy (per standard of care and at the discretion of the investigator) with IFN alpha 3 x 4.5 mIU per week, SC, until progression or withdrawal. Participants could have also received 3 x 500 mg of paracetamol/day during the first weeks of IFN therapy.
|
|---|---|---|
|
Response Duration - Percentage of Participants Event Free at 24 Months
|
60.3 percentage of participants
|
87.7 percentage of participants
|
SECONDARY outcome
Timeframe: Month 24Population: ITTcbcc/FL Population
Time to next treatment was defined as the interval from randomization date to the time when new treatment was needed. Data were analyzed by means of Kaplan-Meier estimators and log-rank tests at the significance level of alpha=5% for difference between the treatment groups.
Outcome measures
| Measure |
Mitoxantrone, Chlorambucil, Prednisolone (MCP)
n=96 Participants
Participants received mitoxantrone 8 mg/m\^2, IV, on Days 1 and 2, chlorambucil 3 x 3 mg/m\^2, PO, every 8 hours on Days 1 through 5, and prednisolone at 25 mg/m\^2, PO on Days 1 through 5. This cycle was repeated at 4-week intervals for a minimum of 6 cycles and a maximum of 8 cycles. After Cycles 2 and 6, participants were assessed for response; participants with no change or with progressive disease (or with minimal response at Cycle 6) were withdrawn from therapy. Participants achieving a CR or PR following induction therapy with MCP were administered maintenance therapy (per standard of care and at the discretion of the investigator) with IFN alpha 3 x 4.5 mIU per week, SC, until progression or withdrawal. Participants could have also received 3 x 500 mg of paracetamol/day during the first weeks of IFN therapy.
|
Rituximab + MCP
n=105 Participants
Participants received rituximab 375 mg/m\^2, IV on Day 1, mitoxantrone 8 mg/m\^2, IV, on Days 3 and 4, chlorambucil 3 x 3 mg/m\^2, PO every 8 hours on Days 3 through 7, and prednisolone 25 mg/m\^2, PO on Days 3 through 7. This cycle was repeated at 4-week intervals for a minimum of 6 cycles and a maximum of 8 cycles. After Cycles 2 and 6, participants were assessed for response; participants with no change or with progressive disease (or with minimal response at Cycle 6) were withdrawn from therapy. Participants achieving a CR or PR following induction therapy with MCP were administered maintenance therapy (per standard of care and at the discretion of the investigator) with IFN alpha 3 x 4.5 mIU per week, SC, until progression or withdrawal. Participants could have also received 3 x 500 mg of paracetamol/day during the first weeks of IFN therapy.
|
|---|---|---|
|
Time to Next Treatment - Percentage of Participants Who Did Not Need New Treatment at 24 Months
|
54.6 percentage of participants
|
72.0 percentage of participants
|
Adverse Events
Mitoxantrone, Chlorambucil, Prednisolone (MCP)
Serious events: 20 serious events
Other events: 146 other events
Deaths: 0 deaths
Rituximab + MCP
Serious events: 18 serious events
Other events: 163 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Mitoxantrone, Chlorambucil, Prednisolone (MCP)
n=177 participants at risk
Participants received mitoxantrone 8 mg/m\^2, IV, on Days 1 and 2, chlorambucil 3 x 3 mg/m\^2, PO, every 8 hours on Days 1 through 5, and prednisolone at 25 mg/m\^2, PO on Days 1 through 5. This cycle was repeated at 4-week intervals for a minimum of 6 cycles and a maximum of 8 cycles. After Cycles 2 and 6, participants were assessed for response; participants with no change or with progressive disease (or with minimal response at Cycle 6) were withdrawn from therapy. Participants achieving a CR or PR following induction therapy with MCP were administered maintenance therapy (per standard of care and at the discretion of the investigator) with IFN alpha 3 x 4.5 mIU per week, SC, until progression or withdrawal. Participants could have also received 3 x 500 mg of paracetamol/day during the first weeks of IFN therapy.
|
Rituximab + MCP
n=183 participants at risk
Participants received rituximab 375 mg/m\^2, IV on Day 1, mitoxantrone 8 mg/m\^2, IV, on Days 3 and 4, chlorambucil 3 x 3 mg/m\^2, PO every 8 hours on Days 3 through 7, and prednisolone 25 mg/m\^2, PO on Days 3 through 7. This cycle was repeated at 4-week intervals for a minimum of 6 cycles and a maximum of 8 cycles. After Cycles 2 and 6, participants were assessed for response; participants with no change or with progressive disease (or with minimal response at Cycle 6) were withdrawn from therapy. Participants achieving a CR or PR following induction therapy with MCP were administered maintenance therapy (per standard of care and at the discretion of the investigator) with IFN alpha 3 x 4.5 mIU per week, SC, until progression or withdrawal. Participants could have also received 3 x 500 mg of paracetamol/day during the first weeks of IFN therapy.
|
|---|---|---|
|
Vascular disorders
Arterial
|
0.00%
0/177
|
0.55%
1/183
|
|
Vascular disorders
Dysrhythmias
|
0.56%
1/177
|
0.00%
0/183
|
|
Vascular disorders
Hypertension
|
0.56%
1/177
|
0.00%
0/183
|
|
Vascular disorders
Ischemia
|
0.56%
1/177
|
0.55%
1/183
|
|
Vascular disorders
Hypotension
|
0.56%
1/177
|
0.00%
0/183
|
|
Vascular disorders
Cardiovascular: other
|
0.56%
1/177
|
0.00%
0/183
|
|
Vascular disorders
Venous
|
0.00%
0/177
|
2.2%
4/183
|
|
Gastrointestinal disorders
Diarrhea
|
0.56%
1/177
|
0.55%
1/183
|
|
Gastrointestinal disorders
Esophagitis/dysphagia
|
0.56%
1/177
|
0.00%
0/183
|
|
Gastrointestinal disorders
Small bowel
|
0.00%
0/177
|
0.55%
1/183
|
|
Gastrointestinal disorders
Gastrointestinal: other
|
1.7%
3/177
|
0.00%
0/183
|
|
Gastrointestinal disorders
Gastrointestinal
|
0.56%
1/177
|
0.00%
0/183
|
|
Gastrointestinal disorders
Gastritis/Ulcer
|
0.56%
1/177
|
0.00%
0/183
|
|
Gastrointestinal disorders
Constipation
|
0.56%
1/177
|
0.00%
0/183
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary edema
|
0.56%
1/177
|
0.00%
0/183
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.56%
1/177
|
1.6%
3/183
|
|
Respiratory, thoracic and mediastinal disorders
Shortness of breath
|
0.56%
1/177
|
0.00%
0/183
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer rel. symptoms: other
|
1.1%
2/177
|
0.00%
0/183
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Second malignancy
|
0.56%
1/177
|
0.55%
1/183
|
|
General disorders
Fever
|
0.56%
1/177
|
0.00%
0/183
|
|
General disorders
Lethargy
|
0.56%
1/177
|
0.00%
0/183
|
|
Infections and infestations
Febrile neutropenia
|
1.1%
2/177
|
3.3%
6/183
|
|
Immune system disorders
Allergy
|
0.00%
0/177
|
0.55%
1/183
|
|
Investigations
Hemoglobin
|
1.7%
3/177
|
1.1%
2/183
|
|
Blood and lymphatic system disorders
Blood/marrow: other
|
0.00%
0/177
|
0.55%
1/183
|
|
Investigations
Granulocytes
|
0.56%
1/177
|
0.00%
0/183
|
|
Investigations
Platelets
|
1.7%
3/177
|
1.6%
3/183
|
|
Investigations
White blood count
|
3.4%
6/177
|
6.6%
12/183
|
|
General disorders
Death from within 30 days of treatment
|
0.56%
1/177
|
0.55%
1/183
|
|
Psychiatric disorders
Mood
|
0.00%
0/177
|
0.55%
1/183
|
|
Nervous system disorders
Neurologic: other
|
1.7%
3/177
|
0.00%
0/183
|
|
Nervous system disorders
Neurologic pain
|
0.56%
1/177
|
0.00%
0/183
|
|
Musculoskeletal and connective tissue disorders
Osseous: other
|
1.1%
2/177
|
0.00%
0/183
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
1.1%
2/177
|
0.55%
1/183
|
|
General disorders
Other
|
1.7%
3/177
|
0.00%
0/183
|
|
Infections and infestations
Infection
|
7.3%
13/177
|
3.8%
7/183
|
|
Investigations
Creatine
|
0.56%
1/177
|
0.00%
0/183
|
|
Renal and urinary disorders
Genitourinary: other
|
0.56%
1/177
|
0.00%
0/183
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
0.00%
0/177
|
0.55%
1/183
|
|
Nervous system disorders
Cerebellar
|
0.56%
1/177
|
0.00%
0/183
|
Other adverse events
| Measure |
Mitoxantrone, Chlorambucil, Prednisolone (MCP)
n=177 participants at risk
Participants received mitoxantrone 8 mg/m\^2, IV, on Days 1 and 2, chlorambucil 3 x 3 mg/m\^2, PO, every 8 hours on Days 1 through 5, and prednisolone at 25 mg/m\^2, PO on Days 1 through 5. This cycle was repeated at 4-week intervals for a minimum of 6 cycles and a maximum of 8 cycles. After Cycles 2 and 6, participants were assessed for response; participants with no change or with progressive disease (or with minimal response at Cycle 6) were withdrawn from therapy. Participants achieving a CR or PR following induction therapy with MCP were administered maintenance therapy (per standard of care and at the discretion of the investigator) with IFN alpha 3 x 4.5 mIU per week, SC, until progression or withdrawal. Participants could have also received 3 x 500 mg of paracetamol/day during the first weeks of IFN therapy.
|
Rituximab + MCP
n=183 participants at risk
Participants received rituximab 375 mg/m\^2, IV on Day 1, mitoxantrone 8 mg/m\^2, IV, on Days 3 and 4, chlorambucil 3 x 3 mg/m\^2, PO every 8 hours on Days 3 through 7, and prednisolone 25 mg/m\^2, PO on Days 3 through 7. This cycle was repeated at 4-week intervals for a minimum of 6 cycles and a maximum of 8 cycles. After Cycles 2 and 6, participants were assessed for response; participants with no change or with progressive disease (or with minimal response at Cycle 6) were withdrawn from therapy. Participants achieving a CR or PR following induction therapy with MCP were administered maintenance therapy (per standard of care and at the discretion of the investigator) with IFN alpha 3 x 4.5 mIU per week, SC, until progression or withdrawal. Participants could have also received 3 x 500 mg of paracetamol/day during the first weeks of IFN therapy.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
21.5%
38/177
|
21.9%
40/183
|
|
Blood and lymphatic system disorders
Leukopenia
|
61.0%
108/177
|
71.0%
130/183
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
40.7%
72/177
|
41.5%
76/183
|
|
Gastrointestinal disorders
Constipation
|
5.6%
10/177
|
8.7%
16/183
|
|
Gastrointestinal disorders
Diarrhoea
|
10.7%
19/177
|
10.4%
19/183
|
|
Gastrointestinal disorders
Dyspepsia
|
3.4%
6/177
|
10.4%
19/183
|
|
Gastrointestinal disorders
Nausea
|
19.8%
35/177
|
19.1%
35/183
|
|
Gastrointestinal disorders
Vomiting
|
5.1%
9/177
|
7.1%
13/183
|
|
General disorders
Chills
|
0.56%
1/177
|
7.7%
14/183
|
|
General disorders
Fatigue
|
3.4%
6/177
|
7.1%
13/183
|
|
General disorders
Pyrexia
|
6.8%
12/177
|
9.8%
18/183
|
|
Infections and infestations
Herpes zoster
|
5.6%
10/177
|
0.55%
1/183
|
|
Infections and infestations
Nasopharyngitis
|
9.0%
16/177
|
10.9%
20/183
|
|
Infections and infestations
Oral herpes
|
6.8%
12/177
|
4.9%
9/183
|
|
Infections and infestations
Urinary tract infection
|
7.3%
13/177
|
3.8%
7/183
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
7.3%
13/177
|
3.3%
6/183
|
|
Nervous system disorders
Dizziness
|
4.0%
7/177
|
6.6%
12/183
|
|
Nervous system disorders
Headache
|
7.3%
13/177
|
7.7%
14/183
|
|
Psychiatric disorders
Initial insomnia
|
2.3%
4/177
|
6.6%
12/183
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.3%
13/177
|
7.7%
14/183
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
5.1%
9/177
|
4.9%
9/183
|
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