search
Back to results

FCM Versus R-FCM Followed by R-Maintenance or Observation Only

Primary Purpose

Lymphoma, Follicular, Lymphoma, Low-Grade, Lymphoma, Intermediate-Grade

Status
Unknown status
Phase
Phase 3
Locations
Germany
Study Type
Interventional
Intervention
FCM
R-FCM
rituximab maintenance
observation only
Sponsored by
Ludwig-Maximilians - University of Munich
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma, Follicular focused on measuring Drug Therapy, Maintenance, rituximab

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria patients with histologically proven stage III/IV centroblastic/centrocytic (FL), centrocytic (MCL)or lymphoplasmacytoid lymphoma (LPIC). relapsed disease after initial chemotherapy or peripheral blood stem cell transplantation two-dimensionally measurable lesion outside a previously irradiated area (osteoblastic bone lesions, ascites, and pleural effusions are not evaluable) age > 18 years Karnofsky-index > 60 life expectancy of at least 3 months effective contraception in female premenopausal patients patient's written informed consent Exclusion Criteria: age < 18 years Karnofsky-index < 60 treatment with fludarabine or mitoxantrone within the preceding three months active auto-immune hemolytic anemia at the start of FCM chemotherapy participation in another clinical trial during the last 4 weeks participation in this study before previous treatment with murine antibodies concurrent diseases which exclude the administration of therapy as outlined by the study protocol non-compensated heart failure dilatative cardiomyopathy coronary heart disease with ST segment depression in ECG myocardial infarction during the last 6 months chronic lung disease with hypoxemia severe non-compensated hypertension severe non-compensated diabetes mellitus renal insufficiency (creatinine > 2.0 mg/dl), not related to lymphoma hepatic insufficiency with transaminase values greater than 3-fold of normal values and/or bilirubin levels > 2.0 mg/dl, not related to lymphoma clinical signs of cerebral dysfunction women during lactation or pregnancy or of childbearing potential not using a reliable contraceptive method severe psychiatric disease serological positivity for HBV, HCV, HIV previous organ transplantation other than autologous peripheral blood stem cell transplantation missing written informed consent or missing written consent for data protection

Sites / Locations

  • German Low Grade Study Group (Glsg)

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Experimental

Other

Other

Arm Label

FCM

R-FCM

Observation only

rituximab maintenance

Arm Description

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Remission rate
Event free interval

Secondary Outcome Measures

Time to Progression
Overall survival
adverse events
serious infectious complications

Full Information

First Posted
April 20, 2006
Last Updated
May 6, 2021
Sponsor
Ludwig-Maximilians - University of Munich
search

1. Study Identification

Unique Protocol Identification Number
NCT00317096
Brief Title
FCM Versus R-FCM Followed by R-Maintenance or Observation Only
Official Title
Treatment of Relapsed CBCC, CC and LPIC Lymphoma With FCM Chemotherapy Alone or in Combination With the Monoclonal Anti CD 20 Antibody Rituximab Followed by Anti-CD 20 Maintenance or Observation Only
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Unknown status
Study Start Date
November 1998 (undefined)
Primary Completion Date
June 2001 (Actual)
Study Completion Date
June 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ludwig-Maximilians - University of Munich

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, Follicular, Lymphoma, Low-Grade, Lymphoma, Intermediate-Grade
Keywords
Drug Therapy, Maintenance, rituximab

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Factorial Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
319 (Actual)

8. Arms, Groups, and Interventions

Arm Title
FCM
Arm Type
Active Comparator
Arm Description
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.
Arm Title
R-FCM
Arm Type
Experimental
Arm Description
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.
Arm Title
Observation only
Arm Type
Other
Arm Description
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.
Arm Title
rituximab maintenance
Arm Type
Other
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
FCM
Intervention Description
Active comparator: Chemotherapy
Intervention Type
Procedure
Intervention Name(s)
R-FCM
Intervention Description
experimental: Chemotherapy with additional rituximab
Intervention Type
Drug
Intervention Name(s)
rituximab maintenance
Intervention Description
2 courses of rituximab maintenance after completion of salvage therapy
Intervention Type
Other
Intervention Name(s)
observation only
Intervention Description
no Intervention after completion of FCM or R-FCM
Primary Outcome Measure Information:
Title
Remission rate
Title
Event free interval
Secondary Outcome Measure Information:
Title
Time to Progression
Title
Overall survival
Title
adverse events
Title
serious infectious complications

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria patients with histologically proven stage III/IV centroblastic/centrocytic (FL), centrocytic (MCL)or lymphoplasmacytoid lymphoma (LPIC). relapsed disease after initial chemotherapy or peripheral blood stem cell transplantation two-dimensionally measurable lesion outside a previously irradiated area (osteoblastic bone lesions, ascites, and pleural effusions are not evaluable) age > 18 years Karnofsky-index > 60 life expectancy of at least 3 months effective contraception in female premenopausal patients patient's written informed consent Exclusion Criteria: age < 18 years Karnofsky-index < 60 treatment with fludarabine or mitoxantrone within the preceding three months active auto-immune hemolytic anemia at the start of FCM chemotherapy participation in another clinical trial during the last 4 weeks participation in this study before previous treatment with murine antibodies concurrent diseases which exclude the administration of therapy as outlined by the study protocol non-compensated heart failure dilatative cardiomyopathy coronary heart disease with ST segment depression in ECG myocardial infarction during the last 6 months chronic lung disease with hypoxemia severe non-compensated hypertension severe non-compensated diabetes mellitus renal insufficiency (creatinine > 2.0 mg/dl), not related to lymphoma hepatic insufficiency with transaminase values greater than 3-fold of normal values and/or bilirubin levels > 2.0 mg/dl, not related to lymphoma clinical signs of cerebral dysfunction women during lactation or pregnancy or of childbearing potential not using a reliable contraceptive method severe psychiatric disease serological positivity for HBV, HCV, HIV previous organ transplantation other than autologous peripheral blood stem cell transplantation missing written informed consent or missing written consent for data protection
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hiddemann Wolfgang, PhD
Organizational Affiliation
University Hospital Großhadern/LMU, Dept. of Medicine III
Official's Role
Principal Investigator
Facility Information:
Facility Name
German Low Grade Study Group (Glsg)
City
Munich
ZIP/Postal Code
D-81377
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
15284112
Citation
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.
Results Reference
result
PubMed Identifier
16946304
Citation
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.
Results Reference
result

Learn more about this trial

FCM Versus R-FCM Followed by R-Maintenance or Observation Only

We'll reach out to this number within 24 hrs