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The aim of this phase III trial is to assess the safety and efficacy of treatment with rituximab in combination with FCM chemotherapy (R-FCM) versus FCM chemotherapy alone for remission induction and to asses the safety and efficacy of rituximab maintenance versus observation only after response to induction therapy. Both questions are addressed in way of a prospective randomized comparison in patients with relapsed FL, MCL and LP lymphoma.
Patients with relapsed centroblastic/centrocytic (FL), centrocytic (MCL)or lymphoplasmacytoid lymphoma are randomly assigned to either FCM chemotherapy alone or to FCM chemotherapy in combination with the monoclonal anti-CD20 antibody rituximab (R-FCM). FCM chemotherapy will be given for 4 cycles in intervals of 4 weeks.
In patients assigned to cytoreductive therapy with FCM plus rituximab, the monoclonal antibody is given as one infusion (375 mg/m2) on the day before the respective FCM course for a total of four applications.
Four weeks after the end of FCM chemotherapy patients with CR or PR are randomly assigned to either no further treatment or maintenance therapy with rituximab. Rituximab will be given 4 times (one infusion per week with 375 mg/m2). After six months rituximab treatment will be repeated with another 4 infusions.
In case of relapse patients will receive an alternative treatment according to the decision of the investigator.
The aim of this phase III trial is to assess the safety and efficacy of treatment with rituximab in combination with FCM chemotherapy versus FCM chemotherapy alone for remission induction and to asses the safety and efficacy of rituximab maintenance versus observation only after response to induction therapy. Both questions are addressed in way of a prospective randomized comparison in patients with relapsed FCL, MCL and LP lymphoma.
Primary objectives of this trial are to compare (1) the remission rates (CR and PR) achieved after FCM plus rituximab versus FCM alone and (2) the progression free interval of rituximab maintenance versus observation only.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| FCM | Active Comparator | All patients underwent a central randomization procedure. Randomization was done by a Computer program stratified for histology, Response to the preceding chemotherapy, and the number of previous chemotherapies using the method of permutuated blocks. The FCM combination comprised: 25 mg/m2 fludarabine per day iv over 30 minutes, days 1 to 3 200 mg/m2 cyclophosphamide per day as a 4-hour-infusion, days 1 to 3 8 mg/m2 mitoxantrone per day iv over 30 minutes, day 1 4 treatment Cycles á 4 weeks per cycle In patients with peripheral lymphocyte Counts more than 20.000/mm3 and/or a large Tumor mass (ie, bulky disease more than 10 cm) a cytoreductive pre-phase could be performed, comprising cyclophosphamide at a dose of 200 mg/m2 as a 1-hour-infusion over 3 to 5 days. |
|
| R-FCM | Experimental | All patients underwent a central randomization procedure. Randomization was done by a Computer program stratified for histology, Response to the preceding chemotherapy, and the number of previous chemotherapies using the method of permutuated blocks. The R-FCM combination comprised: 375 mg/m2 rituximab on the day before the respective FCM course. 25 mg/m2 fludarabine per day iv over 30 minutes, days 1 to 3 200 mg/m2 cyclophosphamide per day as a 4-hour-infusion, days 1 to 3 8 mg/m2 mitoxantrone per day iv over 30 minutes, day 1 4 treatment Cycles á 4 weeks per cycle In patients with peripheral lymphocyte Counts more than 20.000/mm3 and/or a large Tumor mass (ie, bulky disease more than 10 cm) a cytoreductive pre-phase could be performed, comprising cyclophosphamide at a dose of 200 mg/m2 as a 1-hour-infusion over 3 to 5 days. |
|
| Observation only | Other | Patients achieving a complete or partial remission after FCM or R-FCM underwent a subsequent randomization for 2 courses of rituximab to be given 3 and 6 months after completion of salvage therapy versus observation only. This second randomization was stratified for the type of salvage therapy with FCM or R-FCM, the Response to this Treatment (CR or PR), and histology. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| FCM | Procedure | Active comparator: Chemotherapy |
| |
| R-FCM |
| Measure | Description | Time Frame |
|---|---|---|
| Remission rate | ||
| Event free interval |
| Measure | Description | Time Frame |
|---|---|---|
| Time to Progression | ||
| Overall survival | ||
| adverse events |
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Inclusion Criteria
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Hiddemann Wolfgang, PhD | University Hospital Großhadern/LMU, Dept. of Medicine III | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| German Low Grade Study Group (Glsg) | Munich | D-81377 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 15284112 | Result | Forstpointner R, Dreyling M, Repp R, Hermann S, Hanel A, Metzner B, Pott C, Hartmann F, Rothmann F, Rohrberg R, Bock HP, Wandt H, Unterhalt M, Hiddemann W; German Low-Grade Lymphoma Study Group. The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2004 Nov 15;104(10):3064-71. doi: 10.1182/blood-2004-04-1323. Epub 2004 Jul 29. | |
| 16946304 |
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| ID | Term |
|---|---|
| D008224 | Lymphoma, Follicular |
| D008228 | Lymphoma, Non-Hodgkin |
| ID | Term |
|---|---|
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
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|
| rituximab maintenance | Other | Patients achieving a complete or partial remission after FCM or R-FCM underwent a subsequent randomization for 2 courses of rituximab to be given 3 and 6 months after completion of salvage therapy versus observation only. Courses of rituximab consisted of 4 doses of 375 mg/m2 per day given at 4 consecutive weeks. This second randomization was stratified for the type of salvage therapy with FCM or R-FCM, the Response to this Treatment (CR or PR), and histology. |
|
| Procedure |
experimental: Chemotherapy with additional rituximab |
|
| rituximab maintenance | Drug | 2 courses of rituximab maintenance after completion of salvage therapy |
|
| observation only | Other | no Intervention after completion of FCM or R-FCM |
|
| serious infectious complications |
| Result |
| Forstpointner R, Unterhalt M, Dreyling M, Bock HP, Repp R, Wandt H, Pott C, Seymour JF, Metzner B, Hanel A, Lehmann T, Hartmann F, Einsele H, Hiddemann W; German Low Grade Lymphoma Study Group (GLSG). Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: Results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG). Blood. 2006 Dec 15;108(13):4003-8. doi: 10.1182/blood-2006-04-016725. Epub 2006 Aug 31. |
| D008206 |
| Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |