Non-Hodgkin's Lymphoma
Conditions
Brief summary
This study will evaluate the efficacy and safety of MabThera/Rituxan in patients with relapsed low-grade centroblastic centrocytic non-Hodgkin's lymphoma. Patients will receive once-weekly intravenous MabThera/Rituxan for 4 weeks; responding patients will be treated a second time in case of relapse (defined as progression after complete or partial response). The anticipated time on study treatment is \<3 months.
Interventions
DRUGrituximab [MabThera/Rituxan]
375 mg/m2 iv weekly for 4 weeks; for responders to first course of therapy a second course is possible after relapse
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 years of age; * centrocytic centroblastic non-Hodgkin's lymphoma stage III-IV; * relapse after chemotherapy (with or without interferon maintenance therapy).
Exclusion criteria
* primary refractory lymphomas; * more than 3 relapses of centroblastic centrocytic non-Hodgkin's lymphoma; * clinically significant cardiac disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Complete Remission (CR) or Partial Remission (PR) | Treatment start until progression of disease or last available follow-up. The median length of follow-up was 6.6 months (range: 0-97.8 months) | Percentage of participants with a CR, PR at the end of the first cycle of treatment (Week 4). CR was defined as the complete disappearance of all objective disease findings, including enlarged lymph nodes, hepatomegaly, and splenomegaly for at least 4 weeks, and a normalization of blood counts with granulocytes \>1.500/ microliter (µL), hemoglobin (Hb) \>12 grams per deciliter (g/dL), and platelets \>100,000/µL. PR was defined as a less than (\<) 50% regression of all measurable and evaluable lymphoma manifestations (sum of the products of the 2 largest diameters vertical to each other) for at least 4 weeks without the appearance of new manifestations, and normalization of blood counts. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Best Response | Treatment start until progression of disease or last available follow-up. The median length of follow-up was 6.6 months (range: 0-97.8 months) | The median time, in months, from start of the treatment (first application) until best response (PR or CR). |
| Duration of Remission | Treatment start until progression of disease or last available follow-up. The median length of follow-up was 6.6 months (range: 0-97.8 months) | Median time, in months, between the documentation of CR or PR and PD in clinical responders. |
| Number of Participants With a Clinical Response | Treatment start until progression of disease or last available follow-up. The median length of follow-up was 6.6 months (range: 0-97.8 months) | Clinical response was defined as the best response after the first 4 weeks of treatment cycle by the following categories: CR, PR, minor response (MR), stable disease (SD), and progressive disease (PD). CR was defined as the complete disappearance of all objective disease findings, including enlarged lymph nodes, hepatomegaly, and splenomegaly for at least 4 weeks, and a normalization of blood counts with granulocytes \>1,500/μL, Hb \>12 g/dL, and platelets \>100,000/μL. PR was defined as \<50% regression of all measurable and evaluable lymphoma manifestations (sum of the products of the 2 largest diameters vertical to each other) for at least 4 weeks without the appearance of new manifestations, and normalization of blood counts. MR was defined as tumor regression ≥25% and \<50%. SD was defined as tumor regression \<25%, no new manifestations, and progression ≤25%. PD was defined as no new lymphoma associated symptoms or an increase in the size of manifestations by more than 25%. |
| Overall Survival (OS) | Enrollment into study until end of follow-up or death. The median length of follow-up was 6.6 months (range: 0-97.8 months) | OS was defined as the time, in months, between enrollment into the study and death, due to any cause. Participants who were not reported as having died at the time of the analysis were censored using the date they were last known to be alive. |
| Number of Participants With a Clinical Response to Re-Treatment | First application in the second treatment cycle until progression of disease. The median length of follow-up was 4.6 months (range: 0.5-20.6 months). | Clinical response was defined as the best response after the second 4 weeks of treatment cycle by the following categories: CR, PR, MR, SD, and PD. CR was defined as the complete disappearance of all objective disease findings, including enlarged lymph nodes, hepatomegaly, and splenomegaly for at least 4 weeks, and a normalization of blood counts with granulocytes \>1,500/μL, Hb \>12 g/dL, and platelets \>100,000/μL. PR was defined as \<50% regression of all measurable and evaluable lymphoma manifestations (sum of the products of the 2 largest diameters vertical to each other) for at least 4 weeks without the appearance of new manifestations, and normalization of blood counts. MR was defined as tumor regression ≥25% and \<50%. SD was defined as tumor regression \<25%, no new manifestations, and progression ≤25%. PD was defined as no new lymphoma associated symptoms or an increase in the size of manifestations by more than 25%. |
| Time to Progression | Treatment start until progression of disease or last available follow-up. The median length of follow-up was 6.6 months (range: 0-97.8 months) | The median time, in months, from the start of treatment (first application) until detection of PD. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rituximab Participants received rituximab, 375 mg/m\^2, IV, over 4 hours, once per week for 4 weeks. Responders were eligible to receive a second course of treatment after relapse. | 38 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Death | 1 |
| Overall Study | Lost to Follow-up | 8 |
| Overall Study | Physician Decision | 2 |
| Overall Study | Protocol Violation | 2 |
| Overall Study | Transformation to high-grade lymphoma | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Rituximab |
|---|---|
| Age, Continuous | 55 years |
| Age, Customized Between 18 and 65 Years | 32 participants |
| Age, Customized Greater Than or Equal to (≥) 65 Years | 6 participants |
| Age, Customized Less Than or Equal to (≤) 18 Years | 0 participants |
| Ann Arbor stage Stage III | 5 participants |
| Ann Arbor stage Stage IV | 33 participants |
| Bone marrow involvement No | 10 participants |
| Bone marrow involvement Yes | 28 participants |
| B-Symptoms Absent | 24 participants |
| B-Symptoms Present | 14 participants |
| Bulky disease No | 28 participants |
| Bulky disease Yes | 10 participants |
| Histological subtype Follicular or centroblastic/centrocytic lymphoma | 32 participants |
| Histological subtype Other | 6 participants |
| Liver involvement No | 32 participants |
| Liver involvement Yes | 6 participants |
| Number of previous therapies 1 previous therapy | 14 participants |
| Number of previous therapies 2 previous therapies | 11 participants |
| Number of previous therapies 3 previous therapies | 13 participants |
| Other extra-nodal lesions No | 30 participants |
| Other extra-nodal lesions Yes | 8 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 38 Participants |
| Region of Enrollment Germany | 38 participants |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 13 Participants |
| Spleen involvement Missing | 1 participants |
| Spleen involvement No | 21 participants |
| Spleen involvement Yes | 16 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 34 / 38 |
| serious Total, serious adverse events | 10 / 38 |
Outcome results
Primary
Percentage of Participants With a Complete Remission (CR) or Partial Remission (PR)
Percentage of participants with a CR, PR at the end of the first cycle of treatment (Week 4). CR was defined as the complete disappearance of all objective disease findings, including enlarged lymph nodes, hepatomegaly, and splenomegaly for at least 4 weeks, and a normalization of blood counts with granulocytes \>1.500/ microliter (µL), hemoglobin (Hb) \>12 grams per deciliter (g/dL), and platelets \>100,000/µL. PR was defined as a less than (\<) 50% regression of all measurable and evaluable lymphoma manifestations (sum of the products of the 2 largest diameters vertical to each other) for at least 4 weeks without the appearance of new manifestations, and normalization of blood counts.
Time frame: Treatment start until progression of disease or last available follow-up. The median length of follow-up was 6.6 months (range: 0-97.8 months)
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab | Percentage of Participants With a Complete Remission (CR) or Partial Remission (PR) | 39.5 percentage of participants |
Secondary
Duration of Remission
Median time, in months, between the documentation of CR or PR and PD in clinical responders.
Time frame: Treatment start until progression of disease or last available follow-up. The median length of follow-up was 6.6 months (range: 0-97.8 months)
Population: Participants in the ITT population with CR or PR after the first treatment cycle.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rituximab | Duration of Remission | 12.7 months |
Secondary
Number of Participants With a Clinical Response
Clinical response was defined as the best response after the first 4 weeks of treatment cycle by the following categories: CR, PR, minor response (MR), stable disease (SD), and progressive disease (PD). CR was defined as the complete disappearance of all objective disease findings, including enlarged lymph nodes, hepatomegaly, and splenomegaly for at least 4 weeks, and a normalization of blood counts with granulocytes \>1,500/μL, Hb \>12 g/dL, and platelets \>100,000/μL. PR was defined as \<50% regression of all measurable and evaluable lymphoma manifestations (sum of the products of the 2 largest diameters vertical to each other) for at least 4 weeks without the appearance of new manifestations, and normalization of blood counts. MR was defined as tumor regression ≥25% and \<50%. SD was defined as tumor regression \<25%, no new manifestations, and progression ≤25%. PD was defined as no new lymphoma associated symptoms or an increase in the size of manifestations by more than 25%.
Time frame: Treatment start until progression of disease or last available follow-up. The median length of follow-up was 6.6 months (range: 0-97.8 months)
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab | Number of Participants With a Clinical Response | CR | 9 participants |
| Rituximab | Number of Participants With a Clinical Response | PR | 6 participants |
| Rituximab | Number of Participants With a Clinical Response | MR | 3 participants |
| Rituximab | Number of Participants With a Clinical Response | SD | 16 participants |
| Rituximab | Number of Participants With a Clinical Response | PD | 2 participants |
| Rituximab | Number of Participants With a Clinical Response | Missing | 2 participants |
Secondary
Number of Participants With a Clinical Response to Re-Treatment
Clinical response was defined as the best response after the second 4 weeks of treatment cycle by the following categories: CR, PR, MR, SD, and PD. CR was defined as the complete disappearance of all objective disease findings, including enlarged lymph nodes, hepatomegaly, and splenomegaly for at least 4 weeks, and a normalization of blood counts with granulocytes \>1,500/μL, Hb \>12 g/dL, and platelets \>100,000/μL. PR was defined as \<50% regression of all measurable and evaluable lymphoma manifestations (sum of the products of the 2 largest diameters vertical to each other) for at least 4 weeks without the appearance of new manifestations, and normalization of blood counts. MR was defined as tumor regression ≥25% and \<50%. SD was defined as tumor regression \<25%, no new manifestations, and progression ≤25%. PD was defined as no new lymphoma associated symptoms or an increase in the size of manifestations by more than 25%.
Time frame: First application in the second treatment cycle until progression of disease. The median length of follow-up was 4.6 months (range: 0.5-20.6 months).
Population: Participants in the ITT population who began a second cycle of treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab | Number of Participants With a Clinical Response to Re-Treatment | CR | 1 participants |
| Rituximab | Number of Participants With a Clinical Response to Re-Treatment | PR | 0 participants |
| Rituximab | Number of Participants With a Clinical Response to Re-Treatment | MR | 0 participants |
| Rituximab | Number of Participants With a Clinical Response to Re-Treatment | SD | 3 participants |
| Rituximab | Number of Participants With a Clinical Response to Re-Treatment | PD | 0 participants |
| Rituximab | Number of Participants With a Clinical Response to Re-Treatment | Missing | 1 participants |
Secondary
Overall Survival (OS)
OS was defined as the time, in months, between enrollment into the study and death, due to any cause. Participants who were not reported as having died at the time of the analysis were censored using the date they were last known to be alive.
Time frame: Enrollment into study until end of follow-up or death. The median length of follow-up was 6.6 months (range: 0-97.8 months)
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rituximab | Overall Survival (OS) | 49.6 months |
Secondary
Time to Best Response
The median time, in months, from start of the treatment (first application) until best response (PR or CR).
Time frame: Treatment start until progression of disease or last available follow-up. The median length of follow-up was 6.6 months (range: 0-97.8 months)
Population: ITT population; only participants with at least one application of study treatment within the first 4 weeks of treatment were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rituximab | Time to Best Response | 1.9 months |
Secondary
Time to Progression
The median time, in months, from the start of treatment (first application) until detection of PD.
Time frame: Treatment start until progression of disease or last available follow-up. The median length of follow-up was 6.6 months (range: 0-97.8 months)
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rituximab | Time to Progression | 6.6 months |